Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment.

RhoC promotes human melanoma invasion in a PI3K/Akt-dependent pathway.

Ruth MC, Xu Y, Maxwell IH, Ahn NG, Norris DA, Shellman YG

Department of Dermatology, University of Colorado Health Science Center at Fitzsimons, Aurora, Colorado 80045, USA.

Overexpression of the small GTPase, RhoC, in various human cancers has been correlated with high metastatic ability and poor prognosis. Rho-kinase (ROCK) is an important effector of Rho GTPases. The oncogenic serine/threonine kinase Akt (also known as PKB) is a downstream effector of phosphatidylinositol-3 kinase (PI3K). Akt activation contributes to the neoplastic phenotype by promoting cell cycle progression, increasing antiapoptotic functions, and enhancing tumor cell invasion. Rho signaling via ROCK has been previously shown either to activate or to downregulate PI3K/Akt. Using a human radial growth phase melanoma cell line, WM35, we have established stable transfectants that overexpress RhoC (called WM35RhoC). We found that overexpression of RhoC increased phosphorylated-Akt (Ser473/474/472, pAkt) expression and promoted cell invasion. Inhibition of RhoC with C3 transferase downregulated pAkt expression and decreased cell invasion in these cells. In addition, inhibition of PI3K, Akt, or ROCK partially decreased invasion. Further, inhibition of PI3K but not ROCK decreased the pAkt level. These results suggest that RhoC promotes invasion in part via activation of a PI3K/Akt pathway, in a manner independent of ROCK signaling. We propose that RhoC promotes melanoma progression via separate mechanisms that regulate the PI3K/Akt pathway and the ROCK signaling pathway.

Published 16 March 2006 in J Invest Dermatol, 126(4): 862-8.
Full-text of this article is available online (may require subscription).

© 2004-2008 Melanoma Research Today. All Rights Reserved.