HOXC11

Gene Summary

Gene:HOXC11; homeobox C11
Aliases: HOX3H
Location:12q13.13
Summary:This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene binds to a promoter element of the lactase-phlorizin hydrolase. It also may play a role in early intestinal development. An alternatively spliced variant encoding a shorter isoform has been described but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:homeobox protein Hox-C11
Source:NCBIAccessed: 10 March, 2017

Ontology:

What does this gene/protein do?
Show (14)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 10 March 2017 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.

  • Cancer Gene Expression Regulation
  • Promoter Regions
  • RTPCR
  • Acute Myeloid Leukaemia
  • Homeobox Genes
  • Breast Cancer
  • Oncogene Fusion Proteins
  • Antineoplastic Agents, Hormonal
  • Homeodomain Proteins
  • Chromosome 12
  • Biomarkers, Tumor
  • Translocation
  • Transcription
  • Oligonucleotide Array Sequence Analysis
  • Treatment Failure
  • Signal Transduction
  • Polymerase Chain Reaction
  • S100 Proteins
  • Chromosome Breakage
  • Cell Proliferation
  • Tamoxifen
  • Chromosome 11
  • Binding Sites
  • Case-Control Studies
  • MCF-7 Cells
  • Nerve Growth Factors
  • Transcription Factors
  • Disease-Free Survival
  • Nuclear Receptor Coactivator 1
  • Carcinogenesis
  • Stomach Cancer
  • S100B
  • HOXC11
  • Drug Resistance
  • Leukemic Gene Expression Regulation
  • Nuclear Pore Complex Proteins
  • Cervical Cancer
  • Chronic Myelogenous Leukemia
  • Messenger RNA
  • Transcriptional Activation
  • Single Nucleotide Polymorphism
Tag cloud generated 10 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

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: HOXC11 (cancer-related)

Mehrian-Shai R, Yalon M, Moshe I, et al.
Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis.
BMC Genomics. 2016; 17:56 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The genetic mechanisms underlying hemangioblastoma development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays and droplet digital PCR analysis to detect copy number variations (CNVs) in total of 45 hemangioblastoma tumors.
RESULTS: We identified 94 CNVs with a median of 18 CNVs per sample. The most frequently gained regions were on chromosomes 1 (p36.32) and 7 (p11.2). These regions contain the EGFR and PRDM16 genes. Recurrent losses were located at chromosome 12 (q24.13), which includes the gene PTPN11.
CONCLUSIONS: Our findings provide the first high-resolution genome-wide view of chromosomal changes in hemangioblastoma and identify 23 candidate genes: EGFR, PRDM16, PTPN11, HOXD11, HOXD13, FLT3, PTCH, FGFR1, FOXP1, GPC3, HOXC13, HOXC11, MKL1, CHEK2, IRF4, GPHN, IKZF1, RB1, HOXA9, and micro RNA, such as hsa-mir-196a-2 for hemangioblastoma pathogenesis. Furthermore, our data implicate that cell proliferation and angiogenesis promoting pathways may be involved in the molecular pathogenesis of hemangioblastoma.

Du M, Wang W, Jin H, et al.
The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population.
Oncotarget. 2015; 6(31):31255-62 [PubMed] Free Access to Full Article Related Publications
The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13-1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation.

Ali A, Creevey L, Hao Y, et al.
Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer.
Breast Cancer Res. 2015; 17:123 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: HOX genes play vital roles in growth and development, however, atypical redeployment of these genes is often associated with steroidal adaptability in endocrine cancers. We previously identified HOXC11 to be an indicator of poor response to hormonal therapy in breast cancer. In this study we aimed to elucidate genes regulated by HOXC11 in the endocrine resistant setting.
METHODS: RNA-sequencing paired with transcription factor motif-mapping was utilised to identify putative HOXC11 target genes in endocrine resistant breast cancer. Validation and functional evaluation of the target gene, prosaposin (PSAP), was performed in a panel of endocrine sensitive and resistant breast cancer cell lines. The clinical significance of this finding was explored in clinical cohorts at both mRNA and protein level.
RESULTS: PSAP was shown to be regulated by HOXC11 in both tamoxifen and aromatase inhibitor (AI) resistant cell lines. Transcript levels of HOXC11 and PSAP correlated strongly in samples of primary breast tumours (r = 0.7692, n = 51). PSAP has previously been reported to activate androgen receptor (AR) in prostate cancer cells. In a panel of breast cancer cell lines it was shown that endocrine resistant cells exhibit innately elevated levels of AR compared to their endocrine sensitive counterparts. Here, we demonstrate that stimulation with PSAP can drive AR recruitment to a hormone response element (HRE) in AI resistant breast cancer cells. Functionally, PSAP promotes cell migration and invasion only in AI resistant cells and not in their endocrine sensitive counterparts. In a cohort of breast cancer patients (n = 34), elevated serum levels of PSAP were found to associate significantly with poor response to endocrine treatment (p = 0.04). Meta-analysis of combined PSAP and AR mRNA are indicative of poor disease-free survival in endocrine treated breast cancer patients (hazard ratio (HR): 2.2, P = 0.0003, n = 661).
CONCLUSION: The HOXC11 target gene, PSAP, is an AR activator which facilitates adaptation to a more invasive phenotype in vitro. These findings have particular relevance to the development of resistance to AI therapy which is an emerging clinical issue. PSAP is a secreted biomarker which has potential in identifying patients failing to exhibit sustained response to hormonal treatment.

Liu YJ, Zhu Y, Yuan HX, et al.
Overexpression of HOXC11 homeobox gene in clear cell renal cell carcinoma induces cellular proliferation and is associated with poor prognosis.
Tumour Biol. 2015; 36(4):2821-9 [PubMed] Related Publications
Novel evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in four clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. The aim of this study was to investigate whether genes of the HOXC cluster might play a role in renal cancer. The expression of HOXC11 was detected through polymerase chain reaction and immunohistochemical staining, and we demonstrated that HOXC11 was significantly higher in renal cell carcinoma (RCC) compared to normal kidney tissue. We further demonstrated that HOXC11 overexpression in HK-2 human epithelial cell line promoted proliferation, whereas downregulation of HOXC11 endogenous levels in human RCC cells (Caki-2 cells) decreased proliferation. In RCC, expression of HOXC11 and Ki67, a marker of proliferation, correlates strongly with each other (r s  = 0.47, p < 0.003). High immunohistochemical expression of HOXC11 was correlated with T stage (p = 0.06), N stage (p = 0.07), disease stage (p = 0.08), and Ki67 expression (p = 0.07), and patients with tumors showing high number of HOXC11-positive cells had shorter overall survival (p = 0.08) and shorter progression-free survival after treatment (p = 0.08) compared with patients with tumors exhibiting low amount of HOXC11-positive cells. Our data suggest that HOXC11 may contribute to RCC carcinogenesis by increasing tumor cell proliferation and imply that HOXC11 may be an important determinant of RCC patient prognosis.

Walsh CA, Bolger JC, Byrne C, et al.
Global gene repression by the steroid receptor coactivator SRC-1 promotes oncogenesis.
Cancer Res. 2014; 74(9):2533-44 [PubMed] Related Publications
Transcriptional control is the major determinant of cell fate. The steroid receptor coactivator (SRC)-1 enhances the activity of the estrogen receptor in breast cancer cells, where it confers cell survival benefits. Here, we report that a global analysis of SRC-1 target genes suggested that SRC-1 also mediates transcriptional repression in breast cancer cells. Combined SRC-1 and HOXC11 ChIPseq analysis identified the differentiation marker, CD24, and the apoptotic protein, PAWR, as direct SRC-1/HOXC11 suppression targets. Reduced expression of both CD24 and PAWR was associated with disease progression in patients with breast cancer, and their expression was suppressed in metastatic tissues. Investigations in endocrine-resistant breast cancer cell lines and SRC-1(-/-)/PyMT mice confirmed a role for SRC-1 and HOXC11 in downregulation of CD24 and PAWR. Through bioinformatic analysis and liquid chromatography/mass spectrometry, we identified AP1 proteins and Jumonji domain containing 2C (JMD2C/KDM4C), respectively, as members of the SRC-1 interactome responsible for transcriptional repression. Our findings deepen the understanding of how SRC-1 controls transcription in breast cancers.

deBlacam C, Byrne C, Hughes E, et al.
HOXC11-SRC-1 regulation of S100beta in cutaneous melanoma: new targets for the kinase inhibitor dasatinib.
Br J Cancer. 2011; 105(1):118-23 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined.
METHODS: Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays.
RESULTS: Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11-SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo.
CONCLUSION: We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.

McIlroy M, McCartan D, Early S, et al.
Interaction of developmental transcription factor HOXC11 with steroid receptor coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer [corrected].
Cancer Res. 2010; 70(4):1585-94 [PubMed] Related Publications
Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used a mass spectrometry-based screen to identify proteins that are associated with the endocrine-resistant phenotype. In this study, we report the identification of a novel pathway of resistance to endocrine therapy involving interactions of the developmental transcription HOXC11 with the steroid receptor coactivator protein SRC-1, which is a strong predictor of reduced disease-free survival in breast cancer patients. HOXC11 and SRC-1 cooperate to regulate expression of the calcium-binding protein S100beta in resistant breast cancer cells. Nuclear HOXC11 and S100beta were found to strongly predict poor disease-free survival in breast cancer patients (n = 560; hazard ratios: 5.79 and 5.82, respectively; P < 0.0001). Elevated serum levels of S100beta detected in patients also predicted reduced disease-free survival (n = 80; hazard ratio: 5.3; P = 0.004). Our findings define a biomolecular interaction network that drives an adaptive response to endocrine therapy with negative consequences for survival in breast cancer.

La Starza R, Brandimarte L, Pierini V, et al.
A NUP98-positive acute myeloid leukemia with a t(11;12)(p15;q13) without HOXC cluster gene involvement.
Cancer Genet Cytogenet. 2009; 193(2):109-11 [PubMed] Related Publications
We report a case of adult acute myeloid leukemia with a new t(11;12)(p15;q13) underlying a NUP98 rearrangement without HOXC cluster gene involvement. We designed a specific double-color double-fusion FISH assay to discriminate between this t(11;12)(p15;q13) and those producing NUP98-HOXC11 or NUP98-HOXC13. Our fluorescence in situ hybridization (FISH) showed that putative candidate partners mapping 600 kilobases centromeric to HOXC were RARG (retinoic acid receptor gamma), MFSD5 (major facilitator superfamily domain containing 5), and ESPL1 (extra spindle pole bodies homolog 1). It is noteworthy that so far only ESPL1 has been implicated in human cancers. This FISH assay is useful for diagnostic screening of NUP98-positive leukemias.

Zhang X, Hamada J, Nishimoto A, et al.
HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.
J Cell Mol Med. 2007 Mar-Apr; 11(2):299-306 [PubMed] Free Access to Full Article Related Publications
HOX genes encode transcription factors that play a key role in morphogenesis and cell differentiation during embryogenesis of animals. Human neuroblastoma cells are known to be chemically induced to differentiate into neuronal or Schwannian cells. In the present study, we investigated the roles of HOX genes in differentiation of GOTO neuroblastoma cells into Schwannian cells. When GOTO cells were grown in the presence of 5-bromo-2'-deoxyuridine (BrdU), they increased the expressions of two HOX genes (HOXC6 and HOXC11) and marker genes for Schwannian cells (S100beta and myelin basic protein). Forced expression of HOXC11 alone or both HOXC6 isoform 1 and HOXC11 induced the expression of S100beta in GOTO cells. In transient transfection experiments, the overexpression of HOXC6 and HOXC11 transactivated the S100beta promoter-reporter construct. Taken together, our results suggest that HOXC6 and HOXC11 are associated with differentiation of GOTO cells into Schwannian cells through the transcriptional activation of S100beta gene.

Bai XT, Gu BW, Yin T, et al.
Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats.
Cancer Res. 2006; 66(9):4584-90 [PubMed] Related Publications
The formation of fusion genes between NUP98 and members of the HOX family represents a critical factor for the genesis of acute leukemia or acute transformation of chronic myeloid leukemia (CML). To gain insights into the molecular mechanisms underlying the leukemogenesis of NUP98-HOX fusion products, we cloned NUP98-PMX1 from a CML-blast crisis patient with t(1;11) as a secondary chromosomal translocation, and functionally studied the fusion products in detail through various molecular and protein biochemical assays. In addition to many interesting features, we have found that the NUP98-PMX1 fusion protein exerts a repressive effect on PMX1 or serum response factor-mediated c-FOS activation, probably through the recruitment of a common corepressor histone deacetylase 1 by FG domains of the NUP98-PMX1 fusion protein. Moreover, we have provided evidence that the FG domains of NUP98-PMX1 and two other NUP98-containing fusion proteins, i.e., NUP98-HOXA9 and NUP98-HOXC11, all exhibit dual binding ability to both CREB binding protein, a coactivator, and histone deacetylase 1, a corepressor. Accordingly, we have hypothesized that this dual binding activity is shared by most, if not all, NUP98-HOX-involved fusion proteins, enabling these fusion proteins to act as both trans-activators and trans-repressors, and contributing to the genesis of acute leukemia or acute transformation of CML.

Makiyama K, Hamada J, Takada M, et al.
Aberrant expression of HOX genes in human invasive breast carcinoma.
Oncol Rep. 2005; 13(4):673-9 [PubMed] Related Publications
HOX genes are known not only as master genes that control the morphogenesis, but also as regulator genes that maintain tissue or organ specificity in the adult body. We hypothesized that dysregulated expression of HOX genes was associated with tumor development and malignant progression such as invasion and metastasis. In this study, we analyzed the expression patterns of 39 HOX genes in human invasive ductal breast cancer tissues and normal tissues by the real-time RT-PCR method. We found 11 HOX genes (HOXA1, A2, A3, A5, A9, C11, D3, D4, D8, D9 and D10) expression levels of which were significantly different between cancerous and normal tissues. All 10 genes except HOXC11 were expressed at lower levels in cancerous tissues than normal tissues. Comparing expression levels of each HOX gene among the different types of cancer tissues, the expression level of HOXB7 was lower in lymph node metastasis-positive cancer tissues than negative cancer tissues; those of HOXD12 and D13 were higher in progesterone receptor-positive cancer tissues than negative cancer tissues; and the expression level of HOXC5 was lower in cancerous tissues with mutated-type p53 than in normal and cancerous tissues with wild-type p53. These results suggest that the aberrant expression of HOX genes is related to the development of breast cancer and malignant behavior of cancer cells.

Park JS, Young Yoon S, Kim JM, et al.
Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray.
Cancer Lett. 2004; 214(1):19-33 [PubMed] Related Publications
The 5-Fluorouracil (5-FU) is an anticancer drug that is widely used in the treatment of cancer. To identify novel genes associated with 5-FU in gastric cancer, the time-dependent expression profiling of genes in response to 5-FU was examined in 5-FU sensitive and/or resistant gastric cancer cell lines using a 'KUGI 14 K cDNA chip' containing 14,081 unigenes obtained from human gastric cancer cell lines and tissues. By this analysis, we obtained 13 genes which are directly associated with sensitivity or resistance to 5-FU. Of these genes, 11 were found to be commonly up-regulated only in the 5-FU sensitive cell lines, and 2 were oppositely regulated in both of 5-FU sensitive and resistant cell lines. These genes were determined to be involved in cell surface, apoptosis, cell cycle and signal transduction. Of these genes, the expression levels of ZFP100, 4F2hc, FLJ11021, CSTF3, PPP1R14A, DDB2, C6orf139, CDKN1A, HOXC11 and FLJ38860 were confirmed by semi-quantitative RT-PCR. In addition, seven genes containing RRMI, UP1 and K-EST0037597 were found to be commonly up-regulated in both cell lines. In addition, the expression of genes such as TP, OPRT, TS and DPD, which have been previously known to be involved in 5-FU metabolism, were examined in both of 5-FU sensitive and resistant cell lines. These results provide not only predictive biomarkers for 5-FU sensitivity or resistance to human gastric cancer, but also a new molecular basis for understanding the mechanism of cellular cytoxicity to 5-FU.

Gu BW, Wang Q, Wang JM, et al.
Major form of NUP98/HOXC11 fusion in adult AML with t(11;12)(p15;q13) translocation exhibits aberrant trans-regulatory activity.
Leukemia. 2003; 17(9):1858-64 [PubMed] Related Publications
Three adult patients with de novo acute myeloid leukemia of distinct subtypes harboring t(11;12)(p15;q13) have been investigated to characterize the genes involved in that translocation. Through molecular cytogenetics, a chromosome break was detected at the 3' part of nucleoporin 98 (NUP98) gene at 11p15. Using rapid amplification of cDNA end, we identified the partner gene at 12q13, HOXC11. Molecular analysis showed that exon 12 of NUP98 was fused in-frame to exon 2 of HOXC11 in all three cases with t(11;12)(p15;q13). Therefore, this type of fusion may represent the major form of the NUP98-HOXC11 chimera so far reported. Moreover, two out of three cases had a confirmed deletion of the 3' part of NUP98 gene and more telomeric region of 11p harboring a group of tumor-suppressor genes. Interestingly, the NUP98-HOXC11 protein when assayed in a GAL4 reporter system, showed an aberrant trans-regulatory activity as compared to the wild-type HOXC11 in both COS-7 and HL-60 cells. Therefore, NUP98-HOXC11 may contribute to the leukemogenesis by interfering with the cellular mechanism of transcriptional regulation.

Taketani T, Taki T, Shibuya N, et al.
Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13).
Cancer Res. 2002; 62(16):4571-4 [PubMed] Related Publications
The NUP98 gene has been reported to be fused to 11 partner genes in hematological malignancies with 11p15 translocations. Among NUP98 fusion partner genes, HOXA and HOXD clusters have been reported thus far; however, no HOXC or HOXB clusters have been reported. We identified a novel NUP98-HOXC11 fusion gene in a pediatric patient with de novo acute myeloid leukemia having t(11;12)(p15;q13). The breakpoint of NUP98 was located within a LINE repetitive sequence (HAL1) in intron 12, and the breakpoint of HOXC11 was located within exon 1, resulting in a NUP98-HOXC11 in-frame fusion transcript containing exon 12 of NUP98 fused to a part of exon 1 of HOXC11 with an 8-bp insertion derived from the intron sequence just 5' of the breakpoint of NUP98. The NUP98-HOXC11 fusion protein consists of the NH2-terminal phenylalanine-glycine repeat motif of NUP98 and the COOH-terminal homeodomain of HOXC11. Although the frequency of HOXC11 expression was not high in leukemia cell lines, its expression was significantly more frequent in myeloid than lymphoid leukemia cell lines. These data suggest that the NUP98-HOXC11 fusion protein plays a role in the pathogenesis of myeloid malignancies.

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Cite this page: Cotterill SJ. HOXC11, Cancer Genetics Web: http://www.cancer-genetics.org/HOXC11.htm Accessed:

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