Gene Summary

Gene:TWIST1; twist family bHLH transcription factor 1
Summary:This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Aug 2017]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:twist-related protein 1
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Homeodomain Proteins
  • Epithelial-Mesenchymal Transition
  • Down-Regulation
  • RT-PCR
  • MicroRNAs
  • Gene Knockdown Techniques
  • Breast Cancer
  • Apoptosis
  • Xylenes
  • Cadherins
  • Messenger RNA
  • Immunohistochemistry
  • TWIST1
  • RNA Interference
  • Nuclear Proteins
  • Transcription Factors
  • Biomarkers, Tumor
  • Chromosome 7
  • Cancer Stem Cells
  • Western Blotting
  • Cancer Gene Expression Regulation
  • Staging
  • siRNA
  • DNA Methylation
  • Oral Cavity Cancer
  • Cell Movement
  • Neoplasm Invasiveness
  • Cell Proliferation
  • CD Antigens
  • Lung Cancer
  • Progression-Free Survival
  • Spheroids, Cellular
  • Colorectal Cancer
  • Signal Transduction
  • Neoplasm Metastasis
  • Transfection
  • BCL2 protein
  • snail family transcription factors
  • Survival Rate
  • Drug Resistance
  • Gene Expression Profiling
  • Promoter Regions
  • Mice, Inbred BALB C
Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (4)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: TWIST1 (cancer-related)

Ardalan Khales S, Abbaszadegan MR, Majd A, Forghanifard MM
Linkage between EMT and stemness state through molecular association between TWIST1 and NY-ESO1 in esophageal squamous cell carcinoma.
Biochimie. 2019; 163:84-93 [PubMed] Related Publications
Aberrant expression of cancer testis antigens (CTAs) is reported in tumors, especially those with stemness properties. A number of CTAs can induce epithelial mesenchymal transition (EMT) process and promote cancer stem cells (CSCs) characteristics. We aimed in this study to analyze the correlation between NY-ESO1 and TWIST1 in esophageal squamous cell carcinoma (ESCC), as well as their impact on EMT process. Gene expression profiling of NY-ESO1 and TWIST1 was performed in 43 esophageal tumors compared to their margin normal tissues of using qRT-PCR, and their correlation with clinicopathological variables of the patients was evaluated. In silico analysis of the NY-ESO1, epithelial and mesenchymal cell markers and also their promoter sequences was executed. ESCC cell lines KYSE-30 and YM-1 were transduced to ectopically express TWIST1 using a retroviral system, followed by qRT-PCR mRNA expression analysis to reveal the probable correlation among TWIST1, NY-ESO1 and EMT markers gene expression. Scratch assay was performed to estimate migration of TWIST1-induced cells. Overexpression of TWIST1 and NY-ESO1 mRNA was observed in 42% and 39.5% (P ˂ 0.05) of tumors, respectively. Expression of the genes was significantly correlated with each other (p = 0.005). TWIST1 and NY-ESO1 overexpression was significantly associated with stage of progression and size of tumors, respectively. A direct association between TWIST1 and NY-ESO1 mRNA expression was confirmed by induced ectopic expression of TWIST1 in ESCC cell lines KYSE-30 and YM-1. TWIST1-induced cells led to increase migration in ESCC cell line. Furthermore, significant up-regulation of EMT markers was observed following ectopic expression of TWIST1 in these cells. Based on our findings, it may be proposed that a vital association is exist between the EMT and the acquisition of cancer stemness state in tumor cells through the TWIST1/NY-ESO1 axis and it can be a critical hallmark in ESCC tumorigenesis.

Herreño AM, Ramírez AC, Chaparro VP, et al.
Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter.
Tumour Biol. 2019; 41(5):1010428319851014 [PubMed] Related Publications
Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-β induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

Dudzik P, Trojan SE, Ostrowska B, et al.
The Epigenetic Modifier 5-Aza-2-deoxycytidine Triggers the Expression of
Anticancer Res. 2019; 39(5):2395-2403 [PubMed] Related Publications
BACKGROUND/AIM: During cancer progression cells undergo epithelial-to-mesenchymal transition (EMT). Although EMT is a complex process, recently, it has been reported that CD146 overexpression in prostate cancer cells is sufficient to induce mesenchymal phenotype. The following study aimed to investigate whether the expression of CD146 is altered by an epigenetic modifier in prostate cancer cells, in vitro.
MATERIALS AND METHODS: Three human prostate cancer cell lines were treated with 5-aza-2-deoxycytidine; the expression of CD146 and EMT-related factors was analyzed by RT-PCR and western Blot. The methylation status of the CD146 promoter area was assessed using bisulfite sequencing.
RESULTS: Our data showed that, the expression of CD146 was evidently increased in all three studied cell lines in response to a demethylating agent, both at the mRNA and protein level, suggesting epigenetic regulation of the analyzed gene. However, there was no methylation in the studied CpG island in CD146 gene promoter. Moreover, the demethylating agent induced the expression of EMT-related transcription factors (SNAI1, SNAI2, TWIST1 and ZEB1), the pattern of which differed among the cell lines, as well as alterations in cell morphology; altogether accounting for the mesenchymal phenotype.
CONCLUSION: The demethylating agent 5-aza-2-deoxycytidine triggers the expression of CD146 in prostate cancer cells independently on the methylation status of the analyzed CpG island fragment in CD146 gene promoter. Moreover, demethylation treatment induces a mesenchymal profile in prostate cancer cells.

Xiong Y, Chen R, Wang L, et al.
Downregulation of miR‑186 promotes the proliferation and drug resistance of glioblastoma cells by targeting Twist1.
Mol Med Rep. 2019; 19(6):5301-5308 [PubMed] Related Publications
Temozolomide (TMZ) is widely used as a chemotherapeutic agent in the treatment of glioma; however, the development of drug resistance remains a major obstacle in the effective treatment of glioblastoma. Increasing evidence has indicated that microRNAs (miRs) are involved in the drug resistance of glioma; however, the role of miR‑186‑5p in the TMZ resistance of glioblastoma remains unknown. In the present study, the role of miR‑186‑5p in the resistance of glioblastoma to TMZ was investigated. mRNA and protein expression levels were detected via reverse transcription‑quantitative PCR and western blot analysis, respectively. It was determined that miR‑186‑5p was significantly downregulated in glioblastoma tissues and cell lines. Additionally, the expression of miR‑186‑5p was decreased, whereas that of Twist1 was upregulated during the development of drug resistance in glioma cells. The introduction of miR‑186 into glioblastoma cells via transfection decreased the proliferation and TMZ resistance of glioblastoma cells, as determined via 5‑ethynyl‑2'‑deoxyuridine and Cell Counting Kit‑8 assays, whereas the inhibition of miR‑186‑5p induced opposing effects. Furthermore, luciferase reporter and expression rescue assays revealed that miR‑186‑5p bound to the 3'‑untranslated region of Twist‑related protein 1 (Twist1). In conclusion, the present study demonstrated that downregulation of miR‑186‑5p may contribute to the proliferation and drug resistance of glioblastoma cells via the regulation of Twist1 expression. These results suggested that miR‑186‑5p may be a novel therapeutic target in the treatment of glioblastoma.

Zhang Q, Mao Z, Sun J
NF-κB inhibitor, BAY11-7082, suppresses M2 tumor-associated macrophage induced EMT potential via miR-30a/NF-κB/Snail signaling in bladder cancer cells.
Gene. 2019; 710:91-97 [PubMed] Related Publications
BACKGROUND: Chronic inflammatory microenvironment has been shown to play a key role in initiating tumorigenesis and facilitating malignant progression. Primary tumors surrounded with and infiltrated by tumor-associated macrophages (TAMs) significantly promote the epithelial-to-mesenchymal transition (EMT) and distant metastasis in urothelial bladder cancer.
METHODS: In this study, we aimed to explore the potential of targeting TAMs for the treatment of malignant bladder cancer.
RESULTS: First, we found a higher number of TAMs, CD68 (pan-macrophage marker), and clever-1 (M2 macrophage marker) was associated with a higher pT category and grade in a cohort of 108 patients. In vitro assays showed that the co-culture of TAMs promoted the metastatic potential in HTB-1 and T24 by up-regulating EMT markers including Snail, VEGF and Vimentin, as well as oncogenic markers such as β-catenin and NF-κB. More importantly, M2 co-cultured HTB-1 and T24 showed an increased level of metastatic microRNA, miR-30. Silencing of miR-30 resulted in the reduced metastatic potential, migration/invasion, in association with the decreased expression of Twist1 and Vimentin. The addition of BAY11-7082 into the TAM/cancer co-culture system significantly reduced the M2 phenotype and tumorigenic properties. Coincidentally, miR-30a level was significantly lowered in the presence of BAY11-7082.
CONCLUSION: Our study demonstrated that AMs promoted metastatic potential of bladder cancer cells via promoting EMT through the increase of miR-30a. BAY11-7082 treatment suppressed both oncogenic and metastatic potential in bladder cancer cells while preventing the M2 polarization of TAMs.

Ding X, Li F, Zhang L
Knockdown of Delta-like 3 restricts lipopolysaccharide-induced inflammation, migration and invasion of A2058 melanoma cells via blocking Twist1-mediated epithelial-mesenchymal transition.
Life Sci. 2019; 226:149-155 [PubMed] Related Publications
AIMS: To investigate the effects and mechanisms of DLL3 in inflammation-mediated A2058 melanoma cell invasion and metastasis.
MATERIALS AND METHODS: Melanoma A2058 cells was stimulated with lipopolysaccharide (LPS), with or without transfection of DLL3 siRNA, or DLL3 overexpression vector, or Twist1 siRNA. Cell migration and invasion were detected by wound healing and transwell invasion assay. The production of inflammatory factors TNF-α and IL-6 was measured by ELISA. The expression of Notch signaling-related molecules was detected by PCR and western blot. The protein expression of MMP1, MMP9, VEGF, DLL3, and EMT-related molecules was tested by western blot.
KEY FINDINGS: LPS treatment increased migration and invasion of A2058 cells, accompanied by increased expression of TNF-α and IL-6. DLL3 was both upregulated in the LPS- or TNF-α-stimulated A2058 cells, and DLL3 knockdown inhibited LPS-induced inflammation, migration and invasion of A2058 cells, accompanied by down-regulation of MMP1, MMP9 and VEGF. Besides, DLL3 knockdown inhibits the expression of Twist1, a key EMT regulating factor, as well as the EMT hallmarks slug, N-cadherin and vimentin. Moreover, Twist1 silence inhibited EMT, and limited LPS-induced migration and invasion of A2058 cells, with decreased expression of MMP1, MMP9 and VEGF and reduced production of TNF-α and IL-6 in LPS-stimulated A2058 cells.
SIGNIFICANCE: Knockdown of DLL3 restricts LPS-induced inflammation, migration and invasion of A2058 melanoma cells via blocking Twist1-mediated EMT. Therefore, targeting DLL3 may be a promising therapeutic strategy against inflammation-aggravated melanoma progression.

Mego M, Karaba M, Minarik G, et al.
Circulating Tumor Cells With Epithelial-to-mesenchymal Transition Phenotypes Associated With Inferior Outcomes in Primary Breast Cancer.
Anticancer Res. 2019; 39(4):1829-1837 [PubMed] Related Publications
BACKGROUND/AIM: Circulating tumor cells (CTCs) comprise a heterogeneous population of cancer cells with different clinical and biological value. The aim of this study was to evaluate the prognostic value of CTCs with an epithelial-mesenchymal transition (EMT) phenotype in primary breast cancer (PBC) patients.
PATIENTS AND METHODS: This study included 427 primary breast cancer patients. RNA extracted from CD45-depleted peripheral blood mononuclear cell (PBMCs) was evaluated for the expression of EMT transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) by quantitative real time polymerase chain reaction (qRT-PCR).
RESULTS: In total, CTC EMT was detected in 77 (18.0%) patients. Patients without detectable CTC EMT in peripheral blood had significantly longer disease-free survival than patients with detectable CTC EMT. The prognostic value of CTC EMT was demonstrated in all subgroups of patients.
CONCLUSION: CTCs with an EMT phenotype have a prognostic value in primary breast cancer.

Hsieh SL, Hsieh S, Lai PY, et al.
Carnosine Suppresses Human Colorectal Cell Migration and Intravasation by Regulating EMT and MMP Expression.
Am J Chin Med. 2019; 47(2):477-494 [PubMed] Related Publications
Carnosine is an endogenous dipeptide found in the vertebrate skeletal muscles that is usually obtained through the diet. To investigate the mechanism by which carnosine regulates the migration and intravasation of human colorectal cancer (CRC) cells, we used cultured HCT-116 cells as an experimental model in this study. We examined HCT-116 cell migratory and intravasive abilities and expression of epithelial-mesenchymal transition (EMT)-associated molecules and matrix metalloproteinases (MMPs) after carnosine treatment. The results showed that both migration and invasion were inhibited in cells treated with carnosine. We found significant decreases in Twist-1 protein levels and increases in E-cadherin protein levels in HCT-116 cells after carnosine exposure. Although plasminogen activator (uPA) and MMP-9 mRNA and protein levels were decreased, TIMP-1 mRNA and protein levels were increased. Furthermore, the cytosolic levels of phosphorylated I

Dubruc E, Allias F, Morel AP, et al.
Gestational trophoblastic neoplasms (GTNs) do not display epithelial-to-mesenchymal transition (EMT) features.
Virchows Arch. 2019; 475(1):121-125 [PubMed] Related Publications
Although epithelial-to-mesenchymal transition (EMT) has been described in the development of complete hydatidiform moles and the invasion of the maternal decidua by trophoblasts during normal human placentation, its implication in gestational trophoblastic neoplasm (GTN) without villi is totally unknown. We studied the immunoexpression of EMT transcription factors (TWIST1, ZEB1, ZEB2), E-cadherin, and vimentin in 18 trophoblastic tumors and pseudo-tumors. Weak nuclear TWIST1 immunostaining was seen in 5% to 10% of all trophoblastic cells, without ZEB1 and ZEB2 nuclear staining. Trophoblastic cells did not express vimentin, and the expression of E-cadherin was maintained in all cases, indicating the absence of EMT features in GTN.

Zhu L, Xi PW, Li XX, et al.
The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression.
J Exp Clin Cancer Res. 2019; 38(1):105 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Metastasis remains the biggest obstacle for breast cancer treatment. Therefore, identification of specific biomarker of metastasis is very necessary. The RNA binding protein 3 (RBMS3) acts as a tumor suppressor in various cancers. Whereas, its role and underlying molecular mechanism in breast cancer is far from elucidated.
METHODS: Quantitative real-time PCR and western blots were carried out to determine the expression of RBMS3 in breast cancer cells and tissues. Transwell and in vivo metastasis assay were conducted to investigate the effects of RBMS3 on migration, invasion and metastasis of breast cancer cells. Transcriptome sequencing was applied to screen out the differential gene expression affected by RBMS3. RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1 mRNA.
RESULTS: RBMS3 was downregulated in breast cancer and ectopic expression of RBMS3 contributed to inhibition of cell migration, invasion in vitro and lung metastasis in vivo. Furthermore, RBMS3 negatively regulated Twsit1 expression via directly binding to 3'-UTR of Twist1 mRNA, and thereby decreased Twist1-induced expression of matrix metalloproteinase 2 (MMP2). Additionally, Twist1-induced cell migration, invasion and lung metastasis could be reversed by the upregulation of RBMS3.
CONCLUSIONS: In summary, our study revealed a novel mechanism of the RBMS3/Twsit1/MMP2 axis in the regulation of invasion and metastasis of breast cancer, which may become a potential molecular marker for breast cancer treatment.

Zmetakova I, Kalinkova L, Smolkova B, et al.
A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease-free survival in low-risk breast cancer patients.
Cancer Sci. 2019; 110(5):1695-1704 [PubMed] Free Access to Full Article Related Publications
A Disintegrin And Metalloprotease 23 (ADAM23), a member of the ADAM family, is involved in neuronal differentiation and cancer. ADAM23 is considered a possible tumor suppressor gene and is frequently downregulated in various types of malignancies. Its epigenetic silencing through promoter hypermethylation was observed in breast cancer (BC). In the present study, we evaluated the prognostic significance of ADAM23 promoter methylation for hematogenous spread and disease-free survival (DFS). Pyrosequencing was used to quantify ADAM23 methylation in tumors of 203 BC patients. Presence of circulating tumor cells (CTC) in their peripheral blood was detected by quantitative RT-PCR. Expression of epithelial (KRT19) or mesenchymal (epithelial-mesenchymal transition [EMT]-inducing transcription factors TWIST1, SNAI1, SLUG and ZEB1) mRNA transcripts was examined in CD45-depleted peripheral blood mononuclear cells. ADAM23 methylation was significantly lower in tumors of patients with the mesenchymal CTC (P = .006). It positively correlated with Ki-67 proliferation, especially in mesenchymal CTC-negative patients (P = .001). In low-risk patients, characterized by low Ki-67 and mesenchymal CTC absence, ADAM23 hypermethylation was an independent predictor of DFS (P = .006). Our results indicate that ADAM23 is likely involved in BC progression and dissemination of mesenchymal CTC. ADAM23 methylation has the potential to function as a novel prognostic marker and therapeutic target.

Ondeck MG, Kumar A, Placone JK, et al.
Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling.
Proc Natl Acad Sci U S A. 2019; 116(9):3502-3507 [PubMed] Free Access to Full Article Related Publications
Breast cancer development is associated with increasing tissue stiffness over years. To more accurately mimic the onset of gradual matrix stiffening, which is not feasible with conventional static hydrogels, mammary epithelial cells (MECs) were cultured on methacrylated hyaluronic acid hydrogels whose stiffness can be dynamically modulated from "normal" (<150 Pascals) to "malignant" (>3,000 Pascals) via two-stage polymerization. MECs form and remain as spheroids, but begin to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening play important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. This conversion depended neither on colony size nor cell density, and MECs did not exhibit "memory" of prior niche when serially cultured through cycles of compliant and stiff matrices. Instead, the transcription factor Twist1, transforming growth factor β (TGFβ), and YAP activation appeared to modulate stiffness-mediated signaling; when stiffness-mediated signals were blocked, collective MEC phenotypes were reduced in favor of single MECs migrating away from spheroids. These data indicate a more complex interplay of time-dependent stiffness signaling, spheroid structure, and soluble cues that regulates MEC plasticity than suggested by previous models.

Goulet CR, Champagne A, Bernard G, et al.
Cancer-associated fibroblasts induce epithelial-mesenchymal transition of bladder cancer cells through paracrine IL-6 signalling.
BMC Cancer. 2019; 19(1):137 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cancer-associated fibroblasts (CAFs), activated by tumour cells, are the predominant type of stromal cells in cancer tissue and play an important role in interacting with neoplastic cells to promote cancer progression. Epithelial-mesenchymal transition (EMT) is a key feature of metastatic cells. However, the mechanism by which CAFs induce EMT program in bladder cancer cells remains unclear.
METHODS: To investigate the role of CAFs in bladder cancer progression, healthy primary bladder fibroblasts (HFs) were induced into CAFs (iCAFs) by bladder cancer-derived exosomes. Effect of conditioned medium from iCAFs (CM
RESULTS: Cancer exosome-treated HFs showed CAFs characteristics with high expression levels of αSMA and FAP. We showed that the CM
CONCLUSIONS: We conclude that CAFs promote aggressive phenotypes of non-invasive bladder cancer cells through an EMT induced by the secretion of IL-6.

Franceschi T, Durieux E, Morel AP, et al.
Role of epithelial-mesenchymal transition factors in the histogenesis of uterine carcinomas.
Virchows Arch. 2019; 475(1):85-94 [PubMed] Related Publications
Several subtypes of high-grade endometrial carcinomas (ECs) contain an undifferentiated component of non-epithelial morphology, including undifferentiated and dedifferentiated carcinomas and carcinosarcomas (CSs). The mechanism by which an EC undergoes dedifferentiation has been the subject of much debate. The epithelial-mesenchymal transition (EMT) is one of the mechanisms implicated in the transdifferentiation of high-grade carcinomas. To improve our understanding of the role of EMT in these tumors, we studied a series of 89 carcinomas including 14 undifferentiated/dedifferentiated endometrial carcinomas (UECs/DECs), 49 CSs (21 endometrial, 29 tubo-ovarian and peritoneal), 17 endometrioid carcinomas (grade 1-3), and 9 high-grade serous carcinomas of the uterus, using a panel of antibodies targeting known epithelial markers (Pan-Keratin AE1/AE3 and E-cadherin), mesenchymal markers (N-cadherin), EMT transcription factors (TFs) (ZEB1, ZEB2, TWIST1), PAX8, estrogen receptors (ER), progesterone receptors (PR), and the p53 protein. At least one of the three EMT markers (more frequently ZEB1) was positive in the sarcomatous component of 98% (n = 48/49) of CSs and 98% (n = 13/14) of the undifferentiated component of UEC/DEC. In addition, 86% of sarcomatous areas of CSs and 79% of the undifferentiated component of UEC/DEC expressed all three EMT-TFs. The expression of these markers was associated with the loss of or reduction in epithelial markers (Pan-keratin, E-cadherin), PAX8, and hormone receptors. In contrast, none of the endometrioid and serous endometrial carcinomas expressed ZEB1, while 6% and 36% of endometrioid and 11% and 25% of serous carcinomas focally expressed ZEB2 and TWIST1, respectively. Although morphologically different, EMT appears to be implicated in the dedifferentiation in both CSs and UEC/DEC. Indeed, we speculate that the occurrence of EMT in a well differentiated endometrioid carcinoma may consecutively lead to a dedifferentiated and undifferentiated carcinoma, while in a type II carcinoma, it may result in a CS.

Qi W, Yang Z, Li H, et al.
The role of Tenascin-C and Twist1 in gastric cancer: cancer progression and prognosis.
APMIS. 2019; 127(2):64-71 [PubMed] Related Publications
The aim of the present study was to identify the relation between Tenascin-C (TNC) and Twist1 and determine their clinical significance in gastric cancer (GC). We analyzed the expression of TNC and Twist1 in 159 GC samples and in 91 non-tumor samples using immunohistochemistry. In this study, TNC expression in stromal fibroblasts of GC was remarkably higher than non-tumor gastric lesions. The expression of TNC in GC stromal fibroblasts was significantly associated with pT stage, lymph node metastasis, distant metastasis. Twist1 expression in stromal fibroblasts of GC was remarkably higher than non-tumor gastric lesions. Twist1 expression in the stromal fibroblasts of GC was associated with tumor size, lymph node metastasis, and clinical stage. Furthermore, TNC expression levels in GC stromal fibroblasts were positively associated with Twist1. The simultaneous expression of TNC and Twist1 was significantly higher in stromal fibroblasts of GC than in noncancerous tissues. The simultaneous expression of TNC and Twist1 in GC stromal fibroblasts was positively associated with tumor location, pT stage, lymph node metastasis and clinical stage. Moreover, patients with co-expression of TNC and Twist1 had a poorer prognosis than either TNC or Twist1 positive in GC. Our study revealed that the simultaneous expression of TNC and Twist1 indicated the poorer prognosis of GC. Co-targeting TNC and Twist1 confer significant clinical advantage, which offers a novel therapeutic target in GC.

Zhao XH, Wang ZR, Chen CL, et al.
Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: Potential role in clinical practice.
World J Gastroenterol. 2019; 25(1):138-150 [PubMed] Free Access to Full Article Related Publications
AIM: To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients.
METHODS: We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes.
RESULTS: CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage (
CONCLUSION: Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.

Li Y, Zhang T, Qin S, et al.
Effects of UPF1 expression on EMT process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist in a hepatocellular carcinoma cell line.
Mol Med Rep. 2019; 19(3):2137-2143 [PubMed] Free Access to Full Article Related Publications
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that HCC has a poor prognosis. In the majority of cases, once metastatic, HCC is incurable. To identify an effective treatment for HCC, it is important to understand the underlying molecular mechanisms of HCC‑associated occurrence, proliferation, metastasis and carcinogenesis. In the present study, the role of Up‑frameshift 1 (UPF1), a potential tumor suppressor, was investigated in the HCC cell lines. The expression levels of UPF1 in an HCC cell line were examined by reverse transcription‑quantitative polymerase chain reaction. The expression levels of 19 key proteins in numerous signaling pathways were detected via protein array analysis in the presence of UPF1 overexpression. The present study further investigated the effects of UPF1 expression levels on the epithelial‑mesenchymal transition (EMT) process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist‑related protein 1 (Twist). The results of the present study revealed that UPF1 was significantly downregulated in an HCC cell line. The majority of the proteins exhibited upregulated expression levels in the presence of UPF1 overexpression in the HCC cell line, Huh‑7. Key proteins, including cluster of differentiation (CD)31 (platelet endothelial cell adhesion molecule‑1), Vimentin, CD44, PCNA, Ki‑67, N‑Cadherin, Survivin, P53, Met and retinoblastoma exhibited a significant association with UPF1. Furthermore, western blotting indicated that the expression levels of N‑cadherin, Vimentin and Twist were notably upregulated while UPF1 was overexpressed; however, E‑cadherin was downregulated and opposing observations were reported with protein array analysis. In summary, E‑cadherin expression levels were regulated by the manifold, and UPF1, a potential tumor suppressor, may promote the EMT process in Huh‑7 HCC cells. The findings of the present study suggested that UPF1 expression levels affected the EMT process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist.

Savci-Heijink CD, Halfwerk H, Hooijer GKJ, et al.
Epithelial-to-mesenchymal transition status of primary breast carcinomas and its correlation with metastatic behavior.
Breast Cancer Res Treat. 2019; 174(3):649-659 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been implicated as an important step in the development of distant metastases. We therefore wished to study EMT status of primary breast carcinomas from patients who during follow-up developed distant metastases.
METHODS: mRNA expression profiles of primary breast carcinoma samples (n = 151) from patients who developed metastatic disease were analyzed and EMT status was designated using a previously described EMT-core signature. EMT status of the primary tumor was correlated to clinicopathological characteristics, molecular subtypes, metastasis pattern, chemotherapy response and survival outcomes. In addition, using immunohistochemistry, the expression levels of several proteins implicated in EMT were studied (CDH1, CDH2, NAT1, SNAI2, TWIST1, VIM, and ZEB1) compared with the designated EMT status and survival.
RESULTS: Utilizing the 130-gene-EMT-core signature, 66.2% of the primary tumors in the current study was assessed as EMT-activated. In contrast to our expectations, analyses revealed that 84.6% of Luminal A tumors, 65.1% of Luminal B tumors, and 55.6% of HER2-like had an activated EMT status, compared to only 25% of the basal-type tumors (p < 0.001). EMT status was not correlated to the pattern of metastatic disease, metastasis-specific survival, and overall survival. Similarly, there was not a significant association between EMT status of the primary tumor and chemotherapy response in the metastatic setting. Immunostaining for NAT1 and TWIST1 correlated with the EMT status (p 0.003 and p 0.047, respectively). Multivariate analyses showed that NAT1 and TWIST1 staining was significantly associated with EMT status regardless of the estrogen receptor status of the tumors (p values: 0.020 and 0.027, respectively).
CONCLUSIONS: The EMT status of breast cancers, as defined by the presence of a core EMT gene expression signature is associated with non-basal-type tumors, but not with the pattern of distant metastasis. Of several potential immunohistochemical EMT markers, only NAT1 and TWIST1 expression levels were associated with the gene expression-based EMT status.

Bulzico D, Pires BRB, DE Faria PAS, et al.
Anticancer Res. 2019; 39(1):173-175 [PubMed] Related Publications
BACKGROUND/AIM: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelial-mesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. The aim of this study was to assess the association among Twist1, fibronectin, vimentin and E-cadherin gene expression in adrenocortical tumor samples.
MATERIALS AND METHODS: Twist1, fibronectin, vimentin and E-cadherin gene expression in 18 adrenal adenomas, 18 ACC, and 24 childhood onset adrenocortical tumors were assessed in formalin-fixed paraffin-embedded tissues. The fold expression was calculated according to the 2
RESULTS: A significant correlation between mRNA levels of Twist1, fibronectin and vimentin was evident. Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin expression.
CONCLUSION: The expression of Twist1, the major regulator of EMT, is directly correlated to the expression of mesenchymal markers fibronectin and vimentin in ACC samples.

Kim J, Ahn S, Kim K, et al.
Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy.
Anticancer Res. 2018; 38(12):6881-6889 [PubMed] Related Publications
AIM: To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT).
PATIENTS AND METHODS: Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial-mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated.
RESULTS: The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003).
CONCLUSION: Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.

Han KY, Chen PN, Hong MC, et al.
Naringenin Attenuated Prostate Cancer Invasion
Anticancer Res. 2018; 38(12):6753-6758 [PubMed] Related Publications
BACKGROUND: Prostate cancer is highly prevalent with a high mortality among males worldwide. Naringenin has been demonstrated to exhibit multiple cellular functions. In this study, we examined the effects of naringenin on prostate cancer.
MATERIALS AND METHODS: Transwell and zymography assays were used to detect cell migration and urokinase plasminogen activator (uPA) activity, respectively. Alternation of protein expression was measured by western blot analysis.
RESULTS: Transwell assay and zymography revealed that naringenin suppressed the migration and invasion of PC-3 cells and uPA activity in proportion to the concentration of naringenin. Western blot analysis indicated that naringenin up-regulated E-cadherin expression, but down-regulated the expression of vimentin, SNAIL family zinc finger 1 (SNAI1), SNAIL family zinc finger 2 (SNAI2), and TWIST family bHLH transcription factor 1 (TWIST1).
CONCLUSION: Naringenin inhibited the migration and invasion of PC-3 cells by reversing expression of proteins involved in epithelial-to-mesenchymal transition and down-regulation of uPA activity. Thus, naringenin may be a promising anti-metastasis agent for prostate cancer.

Wu Y, Xin D, Liu C, Wang F
[SIRT1 participates in epithelial-mesenchymal transition of EC-9706 and Eca-109 cells
Nan Fang Yi Ke Da Xue Xue Bao. 2018; 38(11):1325-1330 [PubMed] Related Publications
OBJECTIVE: To explore the role of SIRT1 in the occurrence of epithelial-mesenchymal transition (EMT) in EC-9706 and Eca-109 cells and the possible mechanism.
METHODS: Three chemically synthesized siRNA targeting SIRT1 were transfected into EC-9706 and Eca-109 cells with the non-transfected cells and cells transfected with the negative siRNAs as controls. Real-time PCR and Western blotting were used to detect the expressions of SIRT1, E-cadherin, vimentin, Snail, Twist1 and ZEB in the cells. Transwell invasion assay and wounding healing assay were used to examine the changes in the invasion and metastasis abilities of the cells after transfection.
RESULTS: EC-9706 and Eca-109 cells transfected with SIRT1 siRNA1 and SIRT1 siRNA3 showed significantly decreased mRNA and protein expressions of SIRT1 (
CONCLUSIONS: SIRT1 participates in the invasion and metastasis of EC-9706 and Eca- 109 cells probably by inducing EMT via regulating the expression of Snail.

Ji Q, Li Y, Zhao Q, et al.
KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression.
Neoplasma. 2019; 66(1):92-100 [PubMed] Related Publications
Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

Matsunuma R, Chan DW, Kim BJ, et al.
DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer.
Proc Natl Acad Sci U S A. 2018; 115(51):E11978-E11987 [PubMed] Free Access to Full Article Related Publications
A Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomic analysis prioritized dihydropyrimidinase-like-3 (DPYSL3) as a multilevel (RNA/protein/phosphoprotein) expression outlier specific to the claudin-low (CLOW) subset of triple-negative breast cancers. A PubMed informatics tool indicated a paucity of data in the context of breast cancer, which further prioritized DPYSL3 for study. DPYSL3 knockdown in DPYSL3-positive ([Formula: see text]) CLOW cell lines demonstrated reduced proliferation, yet enhanced motility and increased expression of epithelial-to-mesenchymal transition (EMT) markers, suggesting that DPYSL3 is a multifunctional signaling modulator. Slower proliferation in DPYSL3-negative ([Formula: see text]) CLOW cells was associated with accumulation of multinucleated cells, indicating a mitotic defect that was associated with a collapse of the vimentin microfilament network and increased vimentin phosphorylation. DPYSL3 also suppressed the expression of EMT regulators SNAIL and TWIST and opposed p21 activated kinase 2 (PAK2)-dependent migration. However, these EMT regulators in turn induce DPYSL3 expression, suggesting that DPYSL3 participates in negative feedback on EMT. In conclusion, DPYSL3 expression identifies CLOW tumors that will be sensitive to approaches that promote vimentin phosphorylation during mitosis and inhibitors of PAK signaling during migration and EMT.

Chea C, Miyauchi M, Inubushi T, et al.
Bovine lactoferrin reverses programming of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition in oral squamous cell carcinoma.
Biochem Biophys Res Commun. 2018; 507(1-4):142-147 [PubMed] Related Publications
Epithelial-to-mesenchymal transition (EMT) is a biological process of invasion and metastasis in cancers, including in oral squamous cell carcinoma (OSCC). However, an effective anticancer drug that directly targets EMT has not yet been discovered. Therefore, we aimed to investigate the repressive effects of bovine lactoferrin (bLF) on EMT to achieve mesenchymal-to-epithelial transition (MET) in OSCC. OSCC cell lines, HOC313 (EMT-induced) and SCCVII (without EMT induction), were treated with bLF. The effects of bLF on EMT in OSCC were identified histologically by haematoxylin and eosin staining and observed morphologically and immunohistochemically using an anti-E-cadherin antibody. Expression levels of E-cadherin and vimentin were investigated using RT-PCR and western blotting. Immuno-expression of E-cadherin was examined in vivo in tumour tissues of C3H/HeN mice, transplanted with SCCVII cells, with or without bLF administration. We found that bLF changed the spindle-like mesenchymal cells to cuboidal-like epithelial cells and enhanced the affinity of membrane-bound E-cadherin in HOC313 cells. The transformation of EMT-MET in HOC313 cells was confirmed by the upregulation of E-cadherin and suppression of vimentin. Moreover, bLF suppressed TWIST expression through downregulation of ERK1/2 phosphorylation. Additionally, the inhibition tumour cell infiltration and increase in E-cadherin expression were observed in xenografts of the mice orally administered with bLF. Thus, based on the results from in vitro and in vivo studies, we concluded that bLF caused the restoration of epithelial properties through MET. Importantly, this finding is novel and is the first report indicating that bLF inhibited EMT and induced MET in OSCC, suggesting that bLF may provide a novel therapeutic strategy in OSCC.

Li Y, Bai M, Xu Y, et al.
TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma.
Cell Physiol Biochem. 2018; 50(5):2004-2016 [PubMed] Related Publications
BACKGROUND/AIMS: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis.
METHODS: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo.
RESULTS: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS).
CONCLUSION: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.

Juskowiak B, Bogacz A, Wolek M, et al.
Expression profiling of genes modulated by rosmarinic acid (RA) in MCF-7 breast cancer cells.
Ginekol Pol. 2018; 89(10):541-545 [PubMed] Related Publications
OBJECTIVES: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells.
MATERIAL AND METHODS: MCF-7 cell cultures were treated with 0.2 μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels.
RESULTS: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p < 0.05), and about 6.5-fold for 0.2 μM DOX + 50 μM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40-75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found.
CONCLUSIONS: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment.

Tang Y, Fan M, Choi YJ, et al.
Sika deer (Cervus nippon) velvet antler extract attenuates prostate cancer in xenograft model.
Biosci Biotechnol Biochem. 2019; 83(2):348-356 [PubMed] Related Publications
The present study determines whether antler extract (AE) possesses inhibitory effects in a prostate cancer (PC) xenograft model and explores the underlying mechanism. After therapeutic intervention for two weeks, AE significantly inhibited prostate cancer xenograft tumor growth by 65.08%, and prostate-specific antigen (PSA) and serum dihydrotestosterone (DHT) levels. However, AE increased the serum testosterone level compared to the vehicle control group. Furthermore, our investigation of the inhibitory effects on angiogenesis and epithelial-to-mesenchymal transition (EMT)-related genes revealed that AE downregulated matrix metalloproteinase 2 (MMP)-2, (MMP)-9, vascular endothelial growth factor (VEGF), zinc finger protein (SNAIL1), twist-related protein 1 (TWIST1), and zinc-finger E-box-binding homeobox 1 (ZEB1) in vivo. In contrast, AE increased tissue inhibitor of MMP (TIMP)-1, (TIMP)-2, and E-cadherin. The results suggest that AE possesses potent anti-PC activity, and this is the first report on the anti-PC effect of AE in vivo.

Wu J, Zhang Y, Cheng R, et al.
Expression of epithelial-mesenchymal transition regulators TWIST, SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis.
Histopathology. 2019; 74(5):780-791 [PubMed] Related Publications
AIMS: To assess the expression of epithelial-mesenchymal transition (EMT) regulators in follicular thyroid tumours.
METHODS AND RESULTS: The expression of E-cadherin (E-CAD) and transcription factors TWIST, SLUG and SNAIL in follicular thyroid tumours was examined by immunohistochemistry in tissue samples, including 18 follicular adenomas (FA), 12 minimally invasive follicular thyroid carcinomas (MI-FTC), 16 widely invasive follicular thyroid carcinomas (WI-FTC), 10 poorly differentiated follicular thyroid carcinomas (PDTC) and six anaplastic thyroid carcinomas (ATC). Metastatic tumour tissues from six of these cases were also examined. The results showed an increasing expression trend of EMT regulators in a panel of follicular tumour cases with a spectrum of morphological subtypes from low- to high-risk malignancy. The expression of EMT regulators was higher in the WI-FTC, PDTC and ATC groups but focal and lower in the FA and MI-FTC groups. Different expression intensity of E-CAD and EMT regulators at the tumour centre part and the invasive front (IF) was observed. The loss of E-CAD and expression of EMT regulators was significantly correlated with distant metastasis and vascular invasion (VI) in the well-differentiated follicular carcinoma (WD-FTC), and six tumours of metastatic sites also showed variables positive for EMT regulators. The disease-free survival analysis showed an apparent relationship between the expression of EMT regulators and the tumour disease-free outcomes in WD-FTC.
CONCLUSIONS: Our study supported the role of EMT in the development of follicular thyroid carcinoma and indicated that EMT regulatory proteins may play an important role in WD-FTC that are widely invasive and exhibit distant metastasis.

Xie ZC, Huang JC, Zhang LJ, et al.
Exploration of the diagnostic value and molecular mechanism of miR‑1 in prostate cancer: A study based on meta‑analyses and bioinformatics.
Mol Med Rep. 2018; 18(6):5630-5646 [PubMed] Free Access to Full Article Related Publications
Prostate cancer (PCa) remains a principal issue to be addressed in male cancer‑associated mortality. Therefore, the present study aimed to examine the clinical value and associated molecular mechanism of microRNA (miR)‑1 in PCa. A meta‑analysis was conducted to evaluate the diagnosis of miR‑1 in PCa via Gene Expression Omnibus and ArrayExpress datasets, The Cancer Genome Atlas miR‑1 expression data and published literature. It was identified that expression of miR‑1 was significantly downregulated in PCa. Decreased miR‑1 expression possessed moderate diagnostic value, with area under the curve, sensitivity, specificity and odds ratio values at 0.73, 0.77, 0.57 and 4.60, respectively. Using bioinformatics methods, it was revealed that a number of pathways, including the 'androgen receptor signaling pathway', 'androgen receptor activity', 'transcription factor binding' and 'protein processing in the endoplasmic reticulum', were important in PCa. A total of seven hub genes, including phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS), cadherin 1 (CDH1), SRC proto‑oncogene, non‑receptor tyrosine kinase, twist family bHLH transcription factor 1 (TWIST1), ZW10 interacting kinetochore protein (ZWINT), PCNA clamp associated factor (KIAA0101) and androgen receptor, among which, five (PAICS, CDH1, TWIST1, ZWINT and KIAA0101) were significantly upregulated and negatively correlated with miR‑1, were identified as key miR‑1 target genes in PCa. Additionally, it was investigated whether miR‑1 and its hub genes were associated with clinical features, including age, tumor status, residual tumor, lymph node metastasis, pathological T stage and prostate specific antigen level. Collectively the results suggest that miR‑1 may be involved in the progression of PCa, and consequently be a promising diagnostic marker. The 'androgen receptor signaling pathway', 'androgen receptor activity', 'transcription factor binding' and 'protein processing in the endoplasmic reticulum' may be crucial interactive pathways in PCa. Furthermore, PAICS, CDH1, TWIST1, ZWINT and KIAA0101 may serve as crucial miR‑1 target genes in PCa.

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