title: RhoC and ROCKs regulate cancer cell interactions with endothelial cells.
abstract: 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.
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Nicolas
authors: N
authors: Reymond
authors: Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7IJ, England, UK.
authors: Jae Hong
authors: JH
authors: Im
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Ritu
authors: R
authors: Garg
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Susan
authors: S
authors: Cox
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Magali
authors: M
authors: Soyer
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Philippe
authors: P
authors: Riou
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK.
authors: Audrey
authors: A
authors: Colomba
authors: Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7IJ, England, UK.
authors: Ruth J
authors: RJ
authors: Muschel
authors: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's, House, Guy's Campus, London SE1 1UL, UK. Electronic address: anne.ridley@kcl.ac.uk.
authors: Anne J
authors: AJ
authors: Ridley
mesh_terms: D002450:Cell Communication; D045744:Cell Line, Tumor; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
keywords: Endothelial cells; ROCKs; Rho GTPases; RhoC; cancer metastasis; cell migration