RhoC and ROCKs regulate cancer cell interactions with endothelial cells.
RhoC and ROCKs regulate cancer cell interactions with endothelial cells.
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DOI：
10.1016/j.molonc.2015.01.004
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发表时间：
2015-06
影响因子：
6.6
通讯作者：
Ridley AJ
中科院分区：
文献类型：
--
作者：
Reymond N;Im JH;Garg R;Cox S;Soyer M;Riou P;Colomba A;Muschel RJ;Ridley AJ
RhoC是Rho GT3家族的成员，其通过刺激癌细胞侵袭性而参与癌症进展。在这里，我们报告RhoC调节癌细胞与血管内皮细胞（EC）的相互作用，这是转移过程中的关键步骤。通过RNAi去除RhoC减少了PC 3前列腺癌细胞与EC的粘附、EC之间的嵌入以及体外跨内皮迁移。激酶ROCK1和ROCK2（两种已知的RhoC下游效应物）的耗竭同样降低了癌症与EC的相互作用。RhoC还在体内调节癌细胞在血管EC上形成的突起的延伸。瞬时RhoC耗竭足以减少早期PC 3细胞在肺中的滞留和体内实验性转移形成。我们的研究结果表明RhoC在癌细胞与血管内皮细胞的相互作用中起着核心作用，这是癌症进展的关键事件。RhoC在癌细胞中起作用，在体外和体内介导它们与内皮细胞的相互作用。RhoC调节癌细胞在跨内皮迁移之前附着于内皮细胞和插入内皮细胞之间。RhoC效应子ROCK1和ROCK2的作用类似于调节癌细胞与内皮细胞的相互作用。瞬时RhoC耗竭足以减少肺血管中的癌细胞存活和转移形成。
RhoC is a member of the Rho GTPase family that is implicated in cancer progression by stimulating cancer cell invasiveness. Here we report that RhoC regulates the interaction of cancer cells with vascular endothelial cells (ECs), a crucial step in the metastatic process. RhoC depletion by RNAi reduces PC3 prostate cancer cell adhesion to ECs, intercalation between ECs as well as transendothelial migration in vitro. Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs. RhoC also regulates the extension of protrusions made by cancer cells on vascular ECs in vivo. Transient RhoC depletion is sufficient to reduce both early PC3 cell retention in the lungs and experimental metastasis formation in vivo. Our results indicate RhoC plays a central role in cancer cell interaction with vascular ECs, which is a critical event for cancer progression. RhoC acts in cancer cells to mediate their interaction with endothelial cells in vitro and in vivo. RhoC regulates cancer cell attachment to and insertion between endothelial cells prior to transendothelial migration. The RhoC effectors ROCK1 and ROCK2 act similarly to regulate cancer cell interaction with endothelial cells. Transient RhoC depletion is sufficient to reduce cancer cell survival in lung blood vessels and metastasis formation.
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影响因子：
8.8
作者：
Brown, M.;Roulson, J-A;Hart, C. A.;Tawadros, T.;Clarke, N. W.
通讯作者：
Clarke, N. W.
影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
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11.2
作者：
Croft, DR;Sahai, E;Olson, MF
通讯作者：
Olson, MF
影响因子：
8
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Arpaia, E.;Blaser, H.;Quintela-Fandino, M.;Duncan, G.;Leong, H. S.;Ablack, A.;Nambiar, S. C.;Lind, E. F.;Silvester, J.;Fleming, C. K.;Rufini, A.;Tusche, M. W.;Bruestle, A.;Ohashi, P. S.;Lewis, J. D.;Mak, T. W.
通讯作者：
Mak, T. W.
影响因子：
8
作者：
Lochhead, P. A.;Wickman, G.;Olson, M. F.
通讯作者：
Olson, M. F.