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 NF kappa B tran scription factor initiates an antiapoptotic response and promotes cell cycle progression through increased cyclin 131 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 NF kappa B 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 NF kappa B 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.