HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression

Yong Li, Fengmei Chao, Bei Huang, Dahai Liu, Jaejik Kim, Shuang Huang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cell-cell adhesion molecule cadherin-11(CDH11) is preferentially expressed in basal-like breast cancer cells and facilitates breast cancer cell migration by promoting small GTPase Rac activity. However, how the expression of CDH11 is regulated in breast cancer cells is not understood. Here, we show that CDH11 is transcriptionally controlled by homeobox C8 (HOXC8) in human breast cancer cells. HOXC8 serves as a CDH11-specific transcription factor and binds to the site of nucleotides -196 to -191 in the CDH11 promoter. Depletion of HOXC8 leads to the decrease in anchorage-independent cell growth, cell migration/invasion and spontaneous metastasis of breast cancer cells; however, suppressed tumorigenic events were fully rescued by ectopic CDH11 expression in HOXC8-knockdown cells. These results indicate that HOXC8 impacts breast tumorigenesis through CDH11. The analysis of publically available human breast tumor microarray gene expression database demonstrates a strong positive linear association between HOXC8 and CDH11 expression (ρ = 0.801, p < 0.001). Survival analysis (Kaplan-Meier method, log-rank test) shows that both high HOXC8 and CDH11 expression correlate with poor recurrence-free survival rate of patients. Together, our study suggests that HOXC8 promotes breast tumorigenesis by maintaining high level of CDH11 expression in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)2596-2607
Number of pages12
JournalOncotarget
Volume5
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Homeobox Genes
Carcinogenesis
Breast
Breast Neoplasms
Cell Movement
osteoblast cadherin
Monomeric GTP-Binding Proteins
Cell Adhesion Molecules
Survival Analysis
Transcription Factors
Survival Rate
Nucleotides
Databases
Neoplasm Metastasis
Gene Expression
Recurrence

Keywords

  • Breast cancer
  • CDH11
  • HOXC8
  • Metastasis
  • Transcription

ASJC Scopus subject areas

  • Oncology

Cite this

HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. / Li, Yong; Chao, Fengmei; Huang, Bei; Liu, Dahai; Kim, Jaejik; Huang, Shuang.

In: Oncotarget, Vol. 5, No. 9, 2014, p. 2596-2607.

Research output: Contribution to journalArticle

Li, Yong ; Chao, Fengmei ; Huang, Bei ; Liu, Dahai ; Kim, Jaejik ; Huang, Shuang. / HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. In: Oncotarget. 2014 ; Vol. 5, No. 9. pp. 2596-2607.
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