RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis.
The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that function in cytoskeletal reorganization, cell migration, and stress fiber and focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma cells to exit the blood and colonize the lungs. However, in vivo confirmation of RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we report the generation of RhoC-deficient mice and show that RhoC is dispensable for embryonic and post-natal development. We demonstrate that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis.
Hakem
Anne
A
Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, M5G 2C1, Canada.
Sanchez-Sweatman
Otto
O
You-Ten
Annick
A
Duncan
Gordon
G
Wakeham
Andrew
A
Khokha
Rama
R
Mak
Tak W
TW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology*; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D018631:ras Proteins; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000075024:rhoC GTP-Binding Protein
C512911:Rhoc protein, mouse; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein