Cancer Res：SOX4调节EMT促进乳腺癌发展

7月11日，Cancer Res杂志在线报道了SOX4通过调节上皮-间质转化（EMT）过程而促进乳腺癌发展，并可作为一项判断预后的新的生物标记。

上皮 - 间质转化（EMT）是一个与乳腺癌的发展和转移有关的发育过程。本研究发现，异位过表达SOX4足以使永生化人类乳腺上皮细胞获得间质组织性状，从而增强细胞迁移和侵袭。此外，这些细胞还获得了上皮干细胞的属性，表现为具有CD44增高/CD24降低特征的细胞亚群。

SOX4正调控已知的EMT诱导因子表达，也激活TGF-β途径，以促进EMT。 SOX4本身在乳腺上皮细胞中被TGF-β所诱导，并且是TGF-β诱导的EMT过程所必须的因素。小鼠移植瘤的实验表明，SOX4与致癌基因Ras合作，促进体内的肿瘤发生。

最后，在人类乳腺癌的临床标本中，科学家发现，SOX4异常过表达。而且，SOX4还与三阴性乳腺癌亚型（ER-/PR-/HER2-）相关。研究结果确定SOX4通过综合调节EMT在乳腺癌进展中发挥重要作用，SOX4作为本病的预后较差的标记基因具有重要的临床意义。

doi:10.1016/j.cell.2011.10.017
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SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression

Jianchao Zhang1,Qian Liang1,Yang Lei1,Min Yao2,Lili Li1,Xiaoge Gao1,Jingxin Feng1,Yu Zhang1,Hongwen Gao2,Dong-Xu Liu3,Jun Lu1, andBaiqu Huang1,*

Epithelial-mesenchymal transition (EMT) is a developmental program, which is associated with breast cancer progression and metastasis. Here we report that ectopic overexpression of SOX4 in immortalized human mammary epithelial cells is sufficient for acquisition of mesenchymal traits, enhanced cell migration and invasion, along with epithelial stem cell properties that defined by the presence of a CD44high/CD24low cell subpopulation. SOX4 positively regulated expression of known EMT inducers, also activating the TGF-β pathway to contribute to EMT. SOX4 itself was induced by TGF-β in mammary epithelial cells and was required for TGF-β-induced EMT. Murine xenograft experiments showed that SOX4 cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in clinical specimens of human breast cancer, we found that SOX4 was abnormally overexpressed and correlated with the triple-negative breast cancer subtype (ER-/PR-/HER2-). Our findings define an important function for SOX4 in the progression of breast cancer by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.