Open AccessRhoC and ROCKs regulate cancer cell interactions with endothelial cells
Author(s) -
Reymond Nicolas,
Im Jae Hong,
Garg Ritu,
Cox Susan,
Soyer Magali,
Riou Philippe,
Colomba Audrey,
Muschel Ruth J.,
Ridley Anne J.
Publication year - 2015
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2015.01.004
Subject(s) - rhoc , rock1 , cancer cell , microbiology and biotechnology , cancer research , metastasis , biology , cell adhesion , cancer , cell , rhoa , chemistry , signal transduction , biochemistry , genetics
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.