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KIF14; kinesin family member 14 (1q32.1)

Gene Summary

Gene:KIF14; kinesin family member 14
Location:1q32.1
Summary:KIF14 is a member of the kinesin superfamily of microtubule-associated motors (see MIM 148760) that play important roles in intracellular transport and cell division (Nakagawa et al., 1997 [PubMed 9275178]).[supplied by OMIM, Mar 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:kinesin-like protein KIF14
HPRD
Source:NCBI
Updated:14 December, 2014

Gene
Ontology:

What does this gene/protein do?
Show (8)

Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 14 December 2014 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.

  • Squamous Cell Carcinoma
  • Sequence Deletion
  • Liver Cancer
  • Chromosome Deletion
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes
  • Trisomy
  • Disease Progression
  • Gene Dosage
  • Immunohistochemistry
  • Ovarian Cancer
  • Retinal Neoplasms
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • Retinoblastoma
  • Cell Cycle Proteins
  • rap1 GTP-Binding Proteins
  • Survival Rate
  • Chromosome 1
  • Cancer Gene Expression Regulation
  • Polymerase Chain Reaction
  • KIF14
  • Lung Cancer
  • RNA Interference
  • Young Adult
  • Breast Cancer
  • Tumor Suppressor Proteins
  • Oncogene Proteins
  • Statistics, Nonparametric
  • siRNA
  • Cell Movement
  • Infant
  • Childhood Cancer
  • RTPCR
  • Cell Proliferation
  • Kinesin
  • Gene Expression Profiling
  • Messenger RNA
  • Adenocarcinoma
  • Tumor Markers
  • Xenograft Models
Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (1)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
RetinoblastomaKIF14 and Retinoblastoma View Publications7

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

Related Links

Latest Publications: KIF14 (cancer-related)

Xu H, Choe C, Shin SH, et al.
Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma.
Exp Mol Med. 2014; 46:e97 [PubMed] Free Access to Full Article Related Publications
Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27(Kip1) protein level specifically increased after KIF14 knockdown. The increase in p27(Kip1) was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27(Kip1) accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27(Kip1) for degradation by the 26S proteasome, leading to accumulation of p27(Kip1). The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.

Related: CDKN1B Liver Cancer


Hung PF, Hong TM, Hsu YC, et al.
The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma.
PLoS One. 2013; 8(4):e61664 [PubMed] Free Access to Full Article Related Publications
The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

Related: CGH Lung Cancer MCAM gene


Ehrlichova M, Mohelnikova-Duchonova B, Hrdy J, et al.
The association of taxane resistance genes with the clinical course of ovarian carcinoma.
Genomics. 2013; 102(2):96-101 [PubMed] Related Publications
Taxane and platinum-based chemotherapy regimens are standard treatment for advanced ovarian carcinoma. Expression levels of putative markers of taxane resistance in carcinoma tissues and paired peritoneal samples (n=55) and in 16 samples of ovaries without signs of carcinoma were compared with clinical data and the patients' time to progression. KIF14, PRC1, CIT and ABCC1 genes were significantly overexpressed in carcinomas when compared with normal ovarian tissues, while ABCB1 and CASP9 expression was decreased. Associations of protein expression of the proliferation marker Ki-67 with KIF14, PRC1, ABCB1 and CASP2 were found. Lastly, it was discovered that ABCB1 and CASP2 levels associated with FIGO stage and that the CIT level associated with the time to progression of ovarian carcinoma patients (P<0.0001). In conclusion, ABCB1, CASP2, KIF14, PRC1 and CIT genes seem to associate with surrogate markers of ovarian carcinoma progression and CIT gene associates with therapy outcome.

Related: Ovarian Cancer


Singel SM, Cornelius C, Batten K, et al.
A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer.
Clin Cancer Res. 2013; 19(8):2061-70 [PubMed] Related Publications
PURPOSE: To identify biomarkers within the breast cancer genome that may predict chemosensitivity in breast cancer.
EXPERIMENTAL DESIGN: We conducted an RNA interference (RNAi) screen within the breast cancer genome for genes whose loss-of-function enhanced docetaxel chemosensitivity in an estrogen receptor-negative, progesterone receptor-negative, and Her2-negative (ER-, PR-, and Her2-, respectively) breast cancer cell line, MDA-MB-231. Top candidates were tested for their ability to modulate chemosensitivity in 8 breast cancer cell lines and to show in vivo chemosensitivity in a mouse xenograft model.
RESULTS: From ranking chemosensitivity of 328 short hairpin RNA (shRNA) MDA-MB-231 cell lines (targeting 133 genes with known somatic mutations in breast cancer), we focused on the top two genes, kinesin family member 14 (KIF14) and talin 1 (TLN1). KIF14 and TLN1 loss-of-function significantly enhanced chemosensitivity in four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, HCC38, HCC1937, and Hs478T) but not in three hormone receptor-positive cell lines (MCF7, T47D, and HCC1428) or normal human mammary epithelial cells (HMEC). Decreased expression of KIF14, but not TLN1, also enhanced docetaxel sensitivity in a Her2-amplified breast cancer cell line, SUM190PT. Higher KIF14 and TLN1 expressions are found in TNBCs compared with the other clinical subtypes. Mammary fat pad xenografts of KIF14- and TLN1-deficient MDA-MB-231 cells revealed reduced tumor mass compared with control MDA-MB-231 cells after chemotherapy. KIF14 expression is also prognostic of relapse-free and overall survival in representative breast cancer expression arrays.
CONCLUSION: KIF14 and TLN1 are modulators of response to docetaxel and potential therapeutic targets in TNBC.

Related: Breast Cancer Docetaxel


Yang T, Zhang XB, Zheng ZM
Suppression of KIF14 expression inhibits hepatocellular carcinoma progression and predicts favorable outcome.
Cancer Sci. 2013; 104(5):552-7 [PubMed] Related Publications
The mitotic kinesin superfamily protein KIF14 is essential for cytokinesis and chromosome segregation and increased KIF14 expression is related to a variety of human cancers. In this study, we investigate KIF14 expression in association with clinical variables and the role of KIF14 during tumorigenesis. We found that KIF14 is overexpressed in most primary hepatocellular carcinoma (HCC) tissues compared with the adjacent normal liver tissues and KIF14 overexpression is associated with tumor grade (P = 0.002), stage (P = 0.013) and poor survival (P < 0.001). Downregulation of KIF14 decreased the capacity of proliferation both in vitro and in vivo. Furthermore, suppression of KIF14 not only decreases cancer cell migration but also induces apoptosis of cells with inactivation of the phosphatidylinositol 3-kinase-Akt signaling pathway. Therefore, our current study indicates that KIF14 promotes HCC carcinogenesis and may serve as a potential therapeutic target for human HCC.

Related: Apoptosis Liver Cancer AKT1


Lagarde P, Przybyl J, Brulard C, et al.
Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas.
J Clin Oncol. 2013; 31(5):608-15 [PubMed] Related Publications
PURPOSE: Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.
PATIENTS AND METHODS: One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.
RESULTS: CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
CONCLUSION: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.

Related: Synovial Sarcoma


Ahmed SM, Thériault BL, Uppalapati M, et al.
KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression.
J Cell Biol. 2012; 199(6):951-67 [PubMed] Free Access to Full Article Related Publications
The small GTPase Rap1 regulates inside-out integrin activation and thereby influences cell adhesion, migration, and polarity. Several Rap1 effectors have been described to mediate the cellular effects of Rap1 in a context-dependent manner. Radil is emerging as an important Rap effector implicated in cell spreading and migration, but the molecular mechanisms underlying its functions are unclear. We report here that the kinesin KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. The depletion of KIF14 led to increased cell spreading, altered focal adhesion dynamics, and inhibition of cell migration and invasion. We also show that Radil is important for breast cancer cell proliferation and for metastasis in mice. Our findings provide evidence that the concurrent up-regulation of Rap1 activity and increased KIF14 levels in several cancers is needed to reach optimal levels of Rap1-Radil signaling, integrin activation, and cell-matrix adhesiveness required for tumor progression.

Related: Breast Cancer Signal Transduction RAP1A


Basavarajappa HD, Corson TW
KIF14 as an oncogene in retinoblastoma: a target for novel therapeutics?
Future Med Chem. 2012; 4(17):2149-52 [PubMed] Related Publications


Related: Retinoblastoma


Wang Q, Wang L, Li D, et al.
Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients.
Cancer Epidemiol. 2013; 37(1):79-84 [PubMed] Related Publications
BACKGROUND & AIM: Human kinesin superfamily proteins (KIFs) are a conserved class of microtubule-dependent molecular motor proteins with adenosine triphosphatase activity and motion characteristics. As a member of KIFs, KIF14 plays an important role in the regulation of cell cycle and mitotic progression. Deregulation of KIF14 has been found in several human malignancies and also has been demonstrated to be involved in tumor progression and related to patient survival. The aim of this study was to investigate the clinicopathological significance of KIF14 expression in glioma.
METHODS: Real-time quantitative RT-PCR assay was performed to detect KIF14 mRNA expression, and Western blot and immunohistochemistry analyses were performed to detect KIF14 protein expression in human gliomas and non-neoplastic brain tissues, respectively. Then, the association of KIF14 immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.
RESULTS: KIF14 mRNA and protein expression were respectively increased 5.5- and 4.2-fold on average in glioma tissues relative to non-neoplastic brain tissues (both P < 0.001). Additionally, both KIF14 mRNA and protein expression increased with ascending pathological grade. Then, the high KIF14 immunostaining in glioma tissues was significantly associated with advanced pathological grade (P = 0.008), low Karnofsky performance score (KPS) (P = 0.02), high mitotic index (P = 0.005) and Ki-67 index (P = 0.008). Furthermore, both univariate and multivariate Cox regression analyses determined that KIF14 overexpression effectively predicted decreased overall survival in patients with gliomas.
CONCLUSIONS: These findings offer the first convinced evidence that KIF14 expression in gliomas is tumor-specific and increased in more aggressive tumors. KIF14 might function as a candidate prognostic marker for human gliomas.


Pajovic S, Corson TW, Spencer C, et al.
The TAg-RB murine retinoblastoma cell of origin has immunohistochemical features of differentiated Muller glia with progenitor properties.
Invest Ophthalmol Vis Sci. 2011; 52(10):7618-24 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Human retinoblastoma arises from an undefined developing retinal cell after inactivation of RB1. This is emulated in a murine retinoblastoma model by inactivation of pRB by retinal-specific expression of simian virus 40 large T-antigen (TAg-RB). Some mutational events after RB1 loss in humans are recapitulated at the expression level in TAg-RB, supporting preclinical evidence that this model is useful for comparative studies between mouse and human. Here, the characteristics of the TAg-RB cell of origin are defined.
METHODS: TAg-RB mice were killed at ages from embryonic day (E)18 to postnatal day (P)35. Tumors were analyzed by immunostaining, DNA copy number PCR, or real-time quantitative RT-PCR for TAg protein, retinal cell type markers, and retinoblastoma-relevant genes.
RESULTS: TAg expression began at P8 in a row of inner nuclear layer cells that increased in number through P21 to P28, when clusters reminiscent of small tumors emerged from cells that escaped a wave of apoptosis. Early TAg-expressing cells coexpressed the developmental marker Chx10 and glial markers CRALBP, clusterin, and carbonic anhydrase II (Car2), but not TuJ1, an early neuronal marker. Emerging tumors retained expression of only Chx10 and carbonic anhydrase II. As with human retinoblastoma, TAg-RB tumors showed decreased Cdh11 DNA copy number and gain of Kif14 and Mycn. It was confirmed that TAg-RB tumors lose expression of tumor suppressor cadherin-11 and overexpress oncogenes Kif14, Dek, and E2f3.
CONCLUSIONS: TAg-RB tumors displayed molecular similarity to human retinoblastoma and origin in a cell with features of differentiated Müller glia with progenitor properties.

Related: Apoptosis CASP3 MKI67 Retinoblastoma RB1


Thériault BL, Pajovic S, Bernardini MQ, et al.
Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer.
Int J Cancer. 2012; 130(8):1844-54 [PubMed] Related Publications
The novel oncogene KIF14 (kinesin family member 14) shows genomic gain and overexpression in many cancers including OvCa (ovarian cancer). We discovered that expression of the mitotic kinesin KIF14 is predictive of poor outcome in breast and lung cancers. We now determine the prognostic significance of KIF14 expression in primary OvCa tumors, and evaluate KIF14 action on OvCa cell tumorigenicity in vitro. Gene-specific multiplex PCR and real-time QPCR were used to measure KIF14 genomic (109 samples) and mRNA levels (122 samples) in OvCa tumors. Association of KIF14 with clinical variables was studied using Kaplan-Meier survival and Cox regression analyses. Cellular effects of KIF14 overexpression (stable transfection) and inhibition (stable shRNA knockdown) were studied by proliferation (cell counts), survival (Annexin V immunocytochemistry) and colony formation (soft-agar growth). KIF14 genomic gain (>2.6 copies) was present in 30% of serous OvCas, and KIF14 mRNA was elevated in 91% of tumors versus normal epithelium. High KIF14 in tumors independently predicted for worse outcome (p = 0.03) with loss of correlation with proliferation marker expression and increased rates of recurrence. Overexpression of KIF14 in OvCa cell lines increased proliferation and colony formation (p < 0.01), whereas KIF14 knockdown induced apoptosis and dramatically reduced colony formation (p < 0.05). Our findings indicate that KIF14 mRNA is an independent prognostic marker in serous OvCa. Dependence of OvCa cells on KIF14 for maintenance of in vitro colony formation suggests a role of KIF14 in promoting a tumorigenic phenotype, beyond its known role in proliferation.

Related: MKI67 Ovarian Cancer PCNA: Proliferating cell nuclear antigen


Markowski J, Oczko-Wojciechowska M, Gierek T, et al.
Gene expression profile analysis in laryngeal cancer by high-density oligonucleotide microarrays.
J Physiol Pharmacol. 2009; 60 Suppl 1:57-63 [PubMed] Related Publications
The assessment of gene expression profile in laryngeal cancer shall allow to implement molecular biology methods in diagnostics, as well as in prognosis of the course of disease. Thus, it may influence the choice of the most optimal decisions in regards to the method of treatment, extent of surgical procedure, or the necessity of adding post-operative radiotherapy. The aim of the project was to analyse the gene expression profile of laryngeal cancer using oligonucleotide microarrays, aiming to derive novel molecular markers for that carcinoma. The study comprised a group of 14 patients (12 males and 2 females) with squamous cell laryngeal carcinoma, diagnosed and surgically treated between 2005 - 2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments. To assess gene expression profile, high density oligonucleotide microarrays (Affymetrix U 133 Plus 2.0) were applied, with over 54 thousand probesets for over 47 thousand transcripts. Four genes, previously not assesed in diagnostic context in laryngeal carcinoma, seemed to be valuable markers of that neoplasm. These are: metalloproteinase ADAM12, cycline-dependent kinase 2 - CDK2, kinesine 14 - KIF14, suppressor 1 of checkpoint - CHES1.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology


Markowski J, Tyszkiewicz T, Jarzab M, et al.
Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma.
Eur Arch Otorhinolaryngol. 2009; 266(10):1501-7 [PubMed] Related Publications
The assessment of gene expression profile in laryngeal cancer allows implementation of molecular biology methods in diagnostics, as well as in prognosticating the course of disease, thus allowing taking most optimal decisions as regards the method of treatment, scope of surgical procedure, or the necessity of adding complementary radiotherapy. The aim of the project was to analyze the gene expression profile in laryngeal cancer using oligonucleotide microarrays, having in mind searching new molecular markers for that carcinoma. The study comprised a group of 43 patients (38 males and 5 females) suffering from squamous cell laryngeal carcinoma, diagnosed and surgically treated in the years 2005-2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments, with the use of columns RNeasy Midi and Mini Kit (Qiagen). For the examination of gene expression profile, oligonucleotide microarrays of high density were used, provided by Affymetrix (U 133 2.0 PLUS) containing over 54,000 probes for over 47,000 transcripts. Four genes previously not examined in that respect in laryngeal carcinoma, occurred to be good markers of the neoplasm. They are: metal-proteinase ADAM12, cyclin-dependent kinase 2-CDK2, kinesin 14-KIF14, suppressor 1 of checkpoint-CHES1. The analysis of gene expression profile allows, in laryngeal carcinoma, to point out to new genes, which in future may become molecular markers of the carcinoma.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology


Abiatari I, DeOliveira T, Kerkadze V, et al.
Consensus transcriptome signature of perineural invasion in pancreatic carcinoma.
Mol Cancer Ther. 2009; 8(6):1494-504 [PubMed] Related Publications
Perineural invasion, the growth of tumor cells along nerves, is a key feature of pancreatic cancer. The cardinal symptom of pancreatic cancer, abdominal pain often radiating to the back, as well as the high frequency of local tumor recurrence following resection are both attributed to the unique ability of pancreatic tumor cells to invade the neuronal system. The molecular mechanisms underlying the neuroaffinity of pancreatic tumors are not completely understood. In this study, we developed a novel method to monitor ex vivo perineural invasion into surgically resected rat vagal nerves by different human pancreatic tumor cell lines. Genome-wide transcriptional analyses were employed to identify the consensus set of genes differentially regulated in all highly nerve-invasive (nerve invasion passage 3) versus less invasive (nerve invasion passage 0) pancreatic tumor cells. The critical involvement of kinesin family member 14 (KIF14) and Rho-GDP dissociation inhibitor beta (ARHGDIbeta) in perineural invasion was confirmed on RNA and protein levels in human pancreatic tumor specimens. We found significant up-regulation of KIF14 and ARHGDIbeta mRNA levels in patients with pancreatic cancer, and both proteins were differentially expressed in tumor cells invading the perineural niche of pancreatic cancer patients as detected by immunohistochemistry. Moreover, functional knockdown of KIF14 and ARHGDIbeta using small interfering RNA resulted in altered basal and/or perineural invasion of pancreatic tumor cells. Our work provides novel insights into the molecular determinants of perineural invasion in pancreatic cancer. The established nerve invasion model and the consensus signature of perineural invasion could be instrumental in the identification of novel therapeutic targets of pancreatic cancer as exemplified by KIF14 and ARHGDIbeta.

Related: Cancer of the Pancreas Pancreatic Cancer


Madhavan J, Mitra M, Mallikarjuna K, et al.
KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association.
Mol Vis. 2009; 15:235-40 [PubMed] Free Access to Full Article Related Publications
PURPOSE: We quantified mRNA expression of candidate genes for proliferation (KIF14 and E2F3) in a large retinoblastoma tumor cohort and associated with disease phenotype.
METHODS: KIF14 and E2F3 mRNA expression was quantified by real time PCR in 57 retinoblastoma (RB) tumors, 3 RB cell lines, and control samples that included 4 each fetal, age-matched, adult retinas. Immunohistochemistry was done to confirm KIF14 and E2F3 protein expression in tumor cells. The mRNA expression levels were correlated with disease phenotypes including the significance of chemotherapy on tumors.
RESULTS: There was statistically significant overexpression of KIF14 and E2F3 mRNA in tumors compared with control retinas (p<0.0001). Further, E2F3 also showed a significant overexpression compared to RB cell lines (p=0.01). Immunohistochemistry confirmed KIF14 and E2F3 protein overexpression in tumor cells. KIF14 had significant mRNA overexpression with older age (p=0.01) in presenting patients and in unilateral RB patients (p=0.04). Chemotherapy-treated tumors showed a significant decrease in KIF14 and E2F3 expression compared to untreated tumors (p<0.01 and 0.001, respectively).
CONCLUSIONS: This report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of RB tumors. The decreased expression in chemotherapy treated cases needs further validation in a large chemotherapy-treated cohort.

Related: E2F3 Retinoblastoma


Szponar A, Zubakov D, Pawlak J, et al.
Three genetic developmental stages of papillary renal cell tumors: duplication of chromosome 1q marks fatal progression.
Int J Cancer. 2009; 124(9):2071-6 [PubMed] Related Publications
Papillary renal cell tumors (RCT) make up a cytomorphologically and biologically heterogeneous group of kidney cancers including renal cell adenomas (RCA) and renal cell carcinomas (RCC). To find genetic markers landmarking the tumor progression, we have evaluated the genetic alterations obtained by karyotyping, chromosomal and array-CGH and compared with the cytological characteristics and biological behavior of 60 papillary RCTs. Based on the genetic and clinical data, we have separated 3 groups of tumors and proposed 3 genetically defined developmental stages of papillary RCTs. Papillary RCAs are characterized by combined trisomy of chromosomes 7 and 17, whereas papillary RCCs displayed additional trisomies of 3q, 8q, 12q, 16q and 20q. In addition to the genetic changes occurring in the second group, the third group of tumors was characterized by 1q gain and 6q, 8p, 9p and 14q losses. Kaplan-Meier analysis revealed a significant association between chromosome 1q gain and deadly outcome of the disease. The cytomorphological variation and size of tumors in the second and third groups did not correlate with the clinical outcome. Therefore, we suggest that our genetic classification system landmarking papillary RCA, papillary RCC without and with progression offer a better system to characterize the tumor biology of clinical significance than a cellular/morphological classification.

Related: Chromosome 1 CGH Kidney Cancer


Kim TM, Yim SH, Shin SH, et al.
Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q.
Int J Cancer. 2008; 123(12):2808-15 [PubMed] Free Access to Full Article Related Publications
To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop useful prognosis predictors, it is necessary to identify biologically relevant genomic alterations in HCC. In our study, we defined recurrently altered regions (RARs) common to many cases of HCCs, which may contain tumor-related genes, using whole-genome array-CGH and explored their associations with the clinicopathologic features. Gene set enrichment analysis was performed to investigate functional implication of RARs. On an average, 23.1% of the total probes were altered per case. Mean numbers of altered probes are significantly higher in high-grade, bigger and microvascular invasion (MVI) positive tumors. In total, 32 RARs (14 gains and 18 losses) were defined and 4 most frequent RARs are gains in 1q21.1-q32.1 (64.5%), 1q32.1-q44 (59.2%), 8q11.21-q24.3 (48.7%) and a loss in 17p13.3-p12 (51.3%). Through focusing on RARs, we identified genes and functional pathways likely to be involved in hepatocarcinogenesis. Among genes in the recurrently gained regions on 1q, expression of KIF14 and TPM3 was significantly increased, suggesting their oncogenic potential in HCC. Some RARs showed the significant associations with the clinical features. Especially, the recurrent loss in 9p24.2-p21.1 and gain in 8q11.21-q24.3 are associated with the high tumor grade and MVI, respectively. Functional analysis showed that cytokine receptor binding and defense response to virus pathways are significantly enriched in high grade-related RARs. Taken together, our results and the strategy of analysis will help to elucidate pathogenesis of HCC and to develop biomarkers for predicting behaviors of HCC.

Related: Chromosome 1 Chromosome 8 Liver Cancer


Dimaras H, Khetan V, Halliday W, et al.
Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma.
Hum Mol Genet. 2008; 17(10):1363-72 [PubMed] Related Publications
Retinoblastoma clinical observations revealed the role of tumor suppressor genes in human cancer, Knudson's 'two-hit' model of cancer induction. We now demonstrate that loss of both RB1 tumor suppressor gene alleles initiates quiescent RB1(-/-) retinomas with low level genomic instability and high expression of the senescence-associated proteins p16(INK4a) and p130. Although retinomas can remain unchanged throughout life, highly proliferative, clonal and aneuploid retinoblastomas commonly emerge, exhibiting altered gene copy number and expression of oncogenes (MYCN, E2F3, DEK, KIF14 and MDM4) and tumor suppressor genes (CDH11, p75(NTR)) and reduced expression of p16(INK4a) and p130. We suggest that RB1 inactivation in developing retina induces genomic instability, but senescence can block transformation at the stage of retinoma. However, stable retinoma is rarely clinically observed because progressive genomic instability commonly leads to highly proliferative retinoblastoma.

Related: MKI67 Retinoblastoma RB1 TP53


Madhavan J, Coral K, Mallikarjuna K, et al.
High expression of KIF14 in retinoblastoma: association with older age at diagnosis.
Invest Ophthalmol Vis Sci. 2007; 48(11):4901-6 [PubMed] Related Publications
PURPOSE: KIF14 a mitotic kinesin gene plays an important role in cytokinesis. Deregulation of KIF14 may be a pathway of tumor progression and results in decreased patient survival as seen in breast tumors. Recently, KIF14, a possible gene that drives gain of chromosome arm 1q (the most commonly gained chromosomal region in retinoblastoma), has been shown to be a strong oncogene candidate overexpressed by more than two orders of magnitude in retinoblastoma. This study was conducted to quantify the expression of KIF14 in human retinoblastoma tumors and correlate it with disease phenotype.
METHODS: KIF14 expression was examined by using real-time RT-PCR in 30 retinoblastoma tumors with age at diagnosis between 3 and 68 months. Two 18-month-old, three adult (55-62 years), and three fetal (one 18 weeks' and another pooled retina of 18 and 20 weeks' gestation) retinas were used as the control. KIF14 expression was normalized to the housekeeping control gene TBP and compared with that in an 18-month-old control retina. The protein expression was confirmed in tumor cells by immunohistochemistry and phenotypic correlation was performed.
RESULTS: KIF14 was expressed between 3- and 207-fold greater than 18-month-old retina in 30 retinoblastoma tumors (P < 0.0001). Immunohistochemistry revealed KIF14 localization to both nucleus and cytoplasm of tumor cells. KIF14 mRNA overexpression correlated significantly with older age at diagnosis (P = 0.006). There was no association with differentiation, invasion, or duration of the disease with KIF14 overexpression.
CONCLUSIONS: Overexpression of KIF14 was confirmed in primary human retinoblastoma and showed that patients with an older age at diagnosis express significantly higher levels of KIF14.

Related: Retinoblastoma


Corson TW, Zhu CQ, Lau SK, et al.
KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer.
Clin Cancer Res. 2007; 13(11):3229-34 [PubMed] Related Publications
PURPOSE: The mitotic kinesin KIF14 is overexpressed in multiple cancers including lung cancer. Therefore, we investigated KIF14 expression in association with clinical variables and the effect of KIF14 on in vitro colony formation in non-small-cell lung carcinoma.
EXPERIMENTAL DESIGN: RNA was extracted from 129 untreated, resected tumors and KIF14 expression was quantified by real-time reverse transcription-PCR. Associations with clinical variables were determined by standard statistical methods. KIF14 expression was knocked down by small interfering RNA in H1299 and HeLa cells; proliferation and growth in soft agar were assayed.
RESULTS: Squamous cell carcinoma had the highest KIF14 level, followed by large-cell undifferentiated carcinoma, then adenocarcinoma (P = 0.002). KIF14 level decreased with differentiation (P = 0.01) but was not associated with pathologic stage, T or N stage, or sex. When dichotomized about the median, KIF14 overexpression significantly decreased disease-free survival (Kaplan-Meier log-rank, P = 0.01) and trended toward decreasing overall survival (P = 0.08). In a univariate Cox proportional hazard regression, increasing KIF14 expression decreased disease-free survival [P = 0.01; hazard ratio, 1.44 (95% confidence interval, 1.09-1.91)]. In a multivariate Cox regression, including stage, differentiation, histology, and tumor purity as covariates, KIF14 overexpression remained an independent prognostic factor for disease-free survival [P = 0.01; hazard ratio, 1.45 (95% confidence interval, 1.09-1.94)]. Knockdown of KIF14 in non-small-cell lung carcinoma and cervical carcinoma cell lines decreased proliferation and colony formation in soft agar.
CONCLUSIONS: KIF14 expression is independently prognostic for disease-free survival in lung cancer and knockdown decreases tumorigenicity in vitro, showing that it is a clinically relevant oncogene and an exciting therapeutic target for further study.

Related: Lung Cancer


Corson TW, Gallie BL
One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma.
Genes Chromosomes Cancer. 2007; 46(7):617-34 [PubMed] Related Publications
The childhood eye cancer retinoblastoma is initiated by the loss of both alleles of the prototypic tumor suppressor gene, RB1. However, a large number of cytogenetic and comparative genomic hybridization (CGH) studies have shown that these M1 and M2 mutational events--although necessary for initiation--are not the only genomic changes in retinoblastoma. Some of these subsequent changes, which we have termed M3 to Mn, are likely crucial for tumor progression not only in retinoblastoma but also in other cancers. Moreover, genes showing genomic change in cancer are more stable markers and, therefore, possible therapeutic targets than genes simply differentially expressed. In this review, we provide the first comprehensive summary of the genomic evidence implicating gain of 1q, 2p, 6p, and 13q, and loss of 16q in retinoblastoma oncogenesis, including karyotype, CGH, and microarray CGH data. We discuss the search for candidate oncogenes and tumor suppressor genes within these regions, including the candidates (KIF14, MDM4, MYCN, E2F3, DEK, CDH11, and others), plus associations between genomic changes and clinical parameters. We also review studies of other regions of the retinoblastoma genome, the epigenetic changes of aberrant methylation of MGMT, RASSF1A, CASP8, and MLH1, and the roles microRNAs might play in this cancer. Although many candidate genes have yet to be functionally validated in retinoblastoma, work in this field lays out a molecular cytogenetic pathway of retinoblastoma development. Candidate cancer genes carry diagnostic, prognostic, and therapeutic implications beyond retinoblastoma.

Related: Retinoblastoma


Bowles E, Corson TW, Bayani J, et al.
Profiling genomic copy number changes in retinoblastoma beyond loss of RB1.
Genes Chromosomes Cancer. 2007; 46(2):118-29 [PubMed] Related Publications
Loss of both RB1 alleles is rate limiting for development of retinoblastoma (RB), but genomic copy number gain or loss may impact oncogene(s) and tumor suppressor genes, facilitating tumor progression. We used quantitative multiplex polymerase chain reaction to profile "hot spot" genomic copy number changes for gain at 1q32.1, 6p22, and MYCN, and loss at 16q22 in 87 primary RB and 7 cell lines. Loss at 16q22 (48%) negatively associated with MYCN gain (18%) (Fisher's exact P = 0.031), gain at 1q32.1 (62%) positively associated with 6p "hot spot" gain (43%) (P = 0.033), and there was a trend for positive association between 1q and MYCN gain (P = 0.095). Cell lines had a higher frequency of MYCN amplification than primary tumors (29% versus 3%; P = 0.043). Novel high-level amplification of 1q32.1 in one primary tumor, confirmed by fluorescence in situ hybridization, strongly supports the presence of oncogene(s) in this region, possibly the mitotic kinesin, KIF14. Gene-specific quantitative multiplex polymerase chain reaction of candidate oncogenes at 1q32.1 (KIF14), 6p22 (E2F3 and DEK), and tumor suppressor genes at 16q22 (CDH11) and 17q21 (NGFR) showed the most common gene gains in RB to be KIF14 in cell lines (80%) and E2F3 in primary tumors (70%). The patterns of gain/loss were qualitatively different in 25 RB compared with 12 primary hepatocellular carcinoma and 12 breast cancer cell lines. Gene specific analysis of one bone marrow metastasis of RB, prechemotherapy and postchemotherapy, showed the typical genomic changes of RB pretreatment, which normalized after chemotherapy.

Related: Retinoblastoma RB1


Corson TW, Gallie BL
KIF14 mRNA expression is a predictor of grade and outcome in breast cancer.
Int J Cancer. 2006; 119(5):1088-94 [PubMed] Related Publications
Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin family member 14) as an overexpressed candidate oncogene in the 1q31.3-1q32.1 minimal region of genomic gain in breast cancer cell lines. KIF14 also showed high expression in other cancers, notably an association with survival in lung tumors. We now report KIF14 expression in 99 primary breast tumors and 10 normal breast controls. Measured by real-time RT-PCR, KIF14 was overexpressed 10-fold on average in tumors relative to normals (t test p = 0.000054); expression increased with grade (ANOVA p = 0.000006). Infiltrating ductal carcinomas had higher KIF14 levels than lobular (p = 0.017), and estrogen receptor (ER) negative tumors had higher KIF14 levels than ER positive tumors (t test p = 0.030). KIF14 expression correlated positively with Ki-67 mRNA level (Spearman r = 0.692, p = 0.000001), fraction of positive nodes (r = 0.227, p = 0.024) and percent invasive cells (r = 0.360, p = 0.0002), and negatively with percent fatty stroma (r = -0.258, p = 0.010) and percent normal epithelium (r = -0.291, p = 0.003). KIF14 expression is thus tumor-specific and increased in more aggressive tumors. Indeed, KIF14 expression predicted overall survival (univariate Cox p = 0.010), with an odds ratio of 3.60 (1.37-9.48), in 50 tumors with available outcome data. KIF14 overexpression also predicted decreased disease-free survival (log-rank p = 0.049). These findings are the first evidence of association between expression of a mitotic kinesin and prognostic variables in breast cancer.

Related: Breast Cancer


Corson TW, Huang A, Tsao MS, Gallie BL
KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers.
Oncogene. 2005; 24(30):4741-53 [PubMed] Related Publications
Gain of chromosome 1q31-1q32 is seen in >50% of retinoblastoma and is common in other tumors. To define the minimal 1q region of gain, we determined genomic copy number by quantitative multiplex PCR of 14 sequence tagged sites (STSs) spanning 1q25.3-1q41. The most frequently gained STS at 1q32.1 (71%; 39 of 55 retinoblastoma) defined a 3.06 Mbp minimal region of gain between flanking markers, containing 14 genes. Of these, only KIF14, a putative chromokinesin, was overexpressed in various cancers by real-time RT-PCR. KIF14 mRNA was expressed in 20/22 retinoblastoma samples 100-1000-fold higher than in retina (t-test P=0.00002); cell lines (n=10) had higher levels than tumors (n=12) (P=0.009). KIF14 protein was overexpressed in retinoblastoma tumors and breast cancer cell lines by immunoblot. KIF14 was expressed in 4/4 breast cancer cell lines 31-92-fold higher than in normal breast tissue, in 5/5 medulloblastoma cell lines 22-79-fold higher than in fetal brain, and in 10/22 primary lung tumors 3-34-fold higher than in normal lung. Patients with lung tumors that overexpress KIF14 showed a trend toward decreased survival. KIF14 may thus be important in oncogenesis, and has promise as a prognostic indicator and therapeutic target.

Related: Breast Cancer Chromosome 1 Lung Cancer Childhood Medulloblastoma / PNET Cancer Prevention and Risk Reduction Retinoblastoma


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Cite this page: Cotterill SJ. KIF14, Cancer Genetics Web: http://www.cancerindex.org/geneweb/KIF14.htm Accessed: date

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