7月11日,，Cancer Res雜志在線報(bào)道了SOX4通過調(diào)節(jié)上皮 - 間質(zhì)轉(zhuǎn)化（EMT）過程而促進(jìn)乳腺癌進(jìn)展,，并可作為一項(xiàng)判斷預(yù)后的新的生物標(biāo)記。
上皮 - 間質(zhì)轉(zhuǎn)化（EMT）是一個與乳腺癌的進(jìn)展和轉(zhuǎn)移有關(guān)的發(fā)育過程,。本研究發(fā)現(xiàn),，異位過表達(dá)SOX4足以使永生化人類乳腺上皮細(xì)胞獲得間質(zhì)組織性狀,，從而增強(qiáng)細(xì)胞遷移和侵襲。此外,，這些細(xì)胞還獲得了上皮干細(xì)胞的屬性,，表現(xiàn)為具有CD44增高/CD24降低特征的細(xì)胞亞群。
SOX4正調(diào)控已知的EMT誘導(dǎo)因子表達(dá),，也激活TGF-β途徑,，以促進(jìn)EMT。 SOX4本身在乳腺上皮細(xì)胞中被TGF-β所誘導(dǎo),，并且是TGF-β誘導(dǎo)的EMT過程所必須的因素。小鼠移植瘤的實(shí)驗(yàn)表明,，SOX4與致癌基因Ras合作,，促進(jìn)體內(nèi)的腫瘤發(fā)生。
最后,，在人類乳腺癌的臨床標(biāo)本中,，科學(xué)家發(fā)現(xiàn)，SOX4異常過表達(dá),。而且,，SOX4還與三陰性乳腺癌亞型（ER-/PR-/HER2-）相關(guān)。研究結(jié)果確定SOX4通過綜合調(diào)節(jié)EMT在乳腺癌進(jìn)展中發(fā)揮重要作用,，SOX4作為本病的預(yù)后較差的標(biāo)記基因具有重要的臨床意義,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
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.
