Increased Rac1b expression sustains colorectal tumor cell survival.

The small GTPase Rac1 can stimulate various signaling pathways that contribute to cell transformation. In particular, the activation of the NFkappaB transcription factor initiates an antiapoptotic response and promotes cell cycle progression through increased cyclin D1 expression. As a potential oncogenic mechanism to up-regulate this pathway, the overexpression of the Rac1b splicing variant was reported in some colorectal tumors. Rac1b exists predominantly in the active GTP-bound state and selectively promotes the pathway leading to NFkappaB activation. Here, we studied the role of endogenous Rac1b in colorectal cancer cells. We found that depletion of Rac1b by small interfering RNAs inhibited endogenous NFkappaB activation and reduced cell viability to 50% within 48 hours. This reduction was due to increased apoptosis, although a reduced G(1)-S progression rate was also observed. These data show, for the first time, that colorectal cells expressing alternative spliced Rac1b also depend on Rac1b signaling to sustain their survival.