RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells.
RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells.
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DOI：
10.1038/onc.2011.636
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发表时间：
2012-11-08
期刊：
影响因子：
8
通讯作者：
Cerione, R. A.
中科院分区：
文献类型：
--
作者：
Li, B.;Antonyak, M. A.;Zhang, J.;Cerione, R. A.
从癌细胞表面脱落的称为微囊泡（MV）的水疱结构能够将致癌货物转移到受体癌细胞以及正常细胞，发送有丝分裂信号，极大地促进肿瘤生长。由于mv在循环中是稳定的，它们也可能在继发性定植和转移中起关键作用。因此，了解mv是如何产生的可能对干扰癌症进展有重要的影响。在这里，我们报道了小GTPase RhoA触发了各种人类癌细胞中MV生物发生所必需的特定信号通路。抑制构成该途径的不同蛋白质的活性可阻断供体癌细胞中的MV生物发生，并阻止细胞培养中的致癌转化以及小鼠肿瘤生长。虽然RhoA经常与人类癌症有关，但这些发现现在强调了这种GTPase在恶性转化中以前未被认识到的作用，并表明阻断MV生物发生可能为干扰恶性转化提供新的方法。
Vesicular structures called microvesicles (MV) that are shed from the surfaces of cancer cells are capable of transferring oncogenic cargo to recipient cancer cells, as well as to normal cells, sending mitogenic signals that greatly enhance tumor growth. Because MVs are stable in the circulation, they also may play a key role in secondary colonization and metastasis. Thus, understanding how MVs are generated could have important consequences for interfering with cancer progression. Here we report that the small GTPase RhoA triggers a specific signaling pathway essential for MV biogenesis in various human cancer cells. Inhibiting the activity of different proteins comprising this pathway blocks MV biogenesis in the donor cancer cells and prevents oncogenic transformation in cell culture as well as tumor growth in mice. While RhoA has often been implicated in human cancer, these findings now highlight a previously unappreciated role for this GTPase in malignant transformation, and demonstrate that blocking MV biogenesis may offer novel approaches for interfering with malignant transformation.
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DOI：
10.1083/jcb.200802081
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fackler OT;Grosse R
通讯作者：
Grosse R
影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
Rho-kinase in Vivo的肌球蛋白磷酸酶的肌球蛋白结合亚基（MB）的磷酸化。
DOI：
10.1083/jcb.147.5.1023
发表时间：
1999-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawano Y;Fukata Y;Oshiro N;Amano M;Nakamura T;Ito M;Matsumura F;Inagaki M;Kaibuchi K
通讯作者：
Kaibuchi K
影响因子：
21.3
作者：
Skog, Johan;Wuerdinger, Tom;van Rijn, Sjoerd;Meijer, Dimphna H.;Gainche, Laura;Sena-Esteves, Miguel;Curry, William T., Jr.;Carter, Bob S.;Krichevsky, Anna M.;Breakefield, Xandra O.
通讯作者：
Breakefield, Xandra O.
影响因子：
11.2
作者：
Di Vizio D;Kim J;Hager MH;Morello M;Yang W;Lafargue CJ;True LD;Rubin MA;Adam RM;Beroukhim R;Demichelis F;Freeman MR
通讯作者：
Freeman MR