HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression
HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression
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HOXC8通过转录促进cadherin-11表达促进乳腺肿瘤发生
DOI：
10.18632/oncotarget.1841
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发表时间：
2014-05-01
期刊：
影响因子：
--
通讯作者：
Huang, Shuang
中科院分区：
文献类型：
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作者：
Li, Yong;Chao, Fengmei;Huang, Shuang
细胞-细胞粘附分子钙粘蛋白-11（CDH 11）优先在基底样乳腺癌细胞中表达，并通过促进小GT3 Rac活性促进乳腺癌细胞迁移。然而，CDH 11在乳腺癌细胞中的表达是如何调节的尚不清楚。在这里，我们表明，CDH 11是转录控制的同源框C8（HOXC 8）在人类乳腺癌细胞。HOXC 8是一种CDH 11特异性转录因子，与CDH 11启动子的-196至-191位核苷酸结合。HOXC 8的耗尽导致乳腺癌细胞的锚定非依赖性细胞生长、细胞迁移/侵袭和自发转移的减少;然而，被抑制的致瘤事件被HOXC 8敲低细胞中的异位CDH 11表达完全拯救。这些结果表明HOXC 8通过CDH 11影响乳腺肿瘤发生。对临床上可获得的人乳腺肿瘤微阵列基因表达数据库的分析表明，HOXC 8和CDH 11表达之间存在强的正线性关联（ρ = 0.801，p < 0.001）。生存分析（Kaplan-Meier法，log-rank检验）显示，HOXC 8和CDH 11的高表达均与患者的低无复发生存率相关。总之，我们的研究表明HOXC 8通过维持乳腺癌细胞中高水平的CDH 11表达来促进乳腺肿瘤发生。
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.