Tumor invasion in the absence of epithelial-mesenchymal transition: Podoplanin-mediated remodeling of the actin cytoskeleton
Tumor invasion in the absence of epithelial-mesenchymal transition: Podoplanin-mediated remodeling of the actin cytoskeleton
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DOI：
10.1016/j.ccr.2006.03.010
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发表时间：
2006-04-01
期刊：
影响因子：
50.3
通讯作者：
Christofori, G
中科院分区：
文献类型：
--
作者：
Wicki, A;Lehembre, F;Christofori, G
podoplanin（一种小粘蛋白样蛋白）的表达在许多人类癌症的侵袭性前沿上调。我们已经研究了podoplanin功能在培养的人乳腺癌细胞，在小鼠模型的胰腺P细胞癌变，并在人类癌症活检。我们的研究结果表明，podoplanin促进肿瘤细胞在体外和体内的侵袭。值得注意的是，上皮标志物的表达和亚细胞定位是不变的，并且间充质标志物在侵袭性表达podoplanin的肿瘤细胞中不被诱导。相反，Podoplanin通过下调小Rho家族GTP酶的活性通过丝状伪足形成诱导集体细胞迁移。总之，podoplanin诱导肿瘤细胞侵袭的替代途径，上皮间质转化（EMT）的情况下。
The expression of podoplanin, a small mucin-like protein, is upregulated in the invasive front of a number of human carcinomas. We have investigated podoplanin function in cultured human breast cancer cells, in a mouse model of pancreatic P cell carcinogenesis, and in human cancer biopsies. Our results indicate that podoplanin promotes tumor cell invasion in vitro and in vivo. Notably, the expression and subcellular localization of epithelial markers are unaltered, and mesenchymal markers are not induced in invasive podoplanin-expressing tumor cells. Rather, podoplanin induces collective cell migration by filopodia formation via the downregulation of the activities of small Rho family GTPases. In conclusion, podoplanin induces an alternative pathway of tumor cell invasion in the absence of epithelial-mesenchymal transition (EMT).