A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.
A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.
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DOI：
10.1016/j.devcel.2008.09.003
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发表时间：
2008-12
影响因子：
11.8
通讯作者：
Gertler, Frank B.
中科院分区：
文献类型：
--
作者：
Philippar, Ulrike;Roussos, Evanthia T.;Oser, Matthew;Yamaguchi, Hideki;Kim, Hyung-Do;Giampieri, Silvia;Wang, Yarong;Goswami, Sumanta;Wyckoff, Jeffrey B.;Lauffenburger, Douglas A.;Sahai, Erik;Condeelis, John S.;Gertler, Frank B.
转移性疾病期间癌症的扩散需要肿瘤细胞破坏控制细胞运动性的正常调节网络以侵入周围组织并向血管和淋巴管迁移。使能（Ena）/血管舒张刺激磷蛋白（VASP）蛋白通过控制组装肌动蛋白网络的几何形状来调节细胞运动。Mena是一种Ena/VASP蛋白，在乳腺癌细胞的侵袭性亚群中上调。此外，Mena被交替剪接以产生侵袭同种型MenaINV。在这里，我们表明Mena和MenaINV在体内和体外促进癌细胞的运动性和侵袭性，并增加肺转移。Mena和MenaINV增强表皮生长因子（EGF）诱导的膜突出并增加肿瘤细胞的基质降解活性。有趣的是，MenaINV在驱动转移和使细胞对EGF依赖性侵袭和突出敏感方面比Mena显著更有效。因此，MenaINV的上调可以使肿瘤细胞能够响应于其他良性EGF刺激水平而侵入。
The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, MenaINV. Here we show that Mena and MenaINV promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and MenaINV potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, MenaINV is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of MenaINV could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.
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影响因子：
64.5
作者：
Gertler, FB;Niebuhr, K;Soriano, P
通讯作者：
Soriano, P
影响因子：
4.8
作者：
Barzik, M;Kotova, TI;Schafer, DA
通讯作者：
Schafer, DA
影响因子：
4.6
作者：
Gates, Julie;Mahaffey, James P.;Peifer, Mark
通讯作者：
Peifer, Mark
影响因子：
7.8
作者：
Mouneimne, Ghassan;Soon, Lilian;DesMarais, Vera;Sidani, Mazen;Song, Xiaoyan;Yip, Shu-Chin;Ghosh, Mousumi;Eddy, Robert;Backer, Jonathan M;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
64.5
作者：
Bear, JE;Loureiro, JJ;Gertler, FB
通讯作者：
Gertler, FB