HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression

// Yong Li 1 , Fengmei Chao 1 , Bei Huang 1 , Dahai Liu 1 , Jaejik Kim 2 , Shuang Huang 3,4 1 Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, Anhui, China 2 Department of Biostatistics, Georgia Regents University, Augusta, GA, USA 3 Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA 4 E-institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai, China Correspondence: Yong Li, email: // Shuang Huang, email: // Keywords : HOXC8, CDH11, breast cancer, transcription, metastasis Received : February 2, 2014 Accepted : March 20, 2014 Published : March 22, 2014 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 ( = 0.801, p < 0.001). Survival analysis (Kaplan-Meier method, log-rank test) show 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.