C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression.
C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression.
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C-kit 诱导上皮间质转化并促进唾液腺样囊性癌进展
DOI：
10.18632/oncotarget.1606
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发表时间：
2014-03-30
期刊：
影响因子：
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通讯作者：
Liang XH
中科院分区：
文献类型：
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作者：
Tang YL;Fan YL;Jiang J;Li KD;Zheng M;Chen W;Ma XR;Geng N;Chen QM;Chen Y;Liang XH
上皮间质转化（EMT）与涎腺腺样囊性癌（ACC）的进展和转移有关。在这里，我们报告说，异位过表达的c-kit在ACC细胞系是足够的收购间充质性状，增强细胞侵袭，沿着干细胞特性定义的CD 133 + /CD 44+细胞亚群的存在。c-kit正调节已知EMT诱导剂的表达，也激活TGF-β以促进EMT。c-kit本身在ACC细胞系中由TGF-β诱导，并且是TGF-β诱导的EMT所必需的。异种移植实验表明，c-kit与致癌Ras协同促进体内肿瘤发生。最后，在人类ACC标本中，我们发现c-kit异常过表达，并与ACC. Our的研究结果定义了一个重要的功能，c-kit在ACC的进展，通过精心策划EMT，他们牵连这个基因产物作为一个标志，在这种疾病的预后不良。
Epithelial–mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133 + /CD44 + cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-β to contribute to EMT. c-kit itself was induced by TGF-β in ACC cell lines and required for TGF-β–induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.