SMAD3 and colorectal carcinoma: We demonstrated that TGFβ signaling can activate PKA by a Smad3-dependent, cAMP independent mechanism in IGF1R-dependent subsets of CRC cells leading to cell death through the disruption of the formation survivin/XIAP complexes which are necessary for caspase 3,7,9 inhibition to block apoptosis [9,13].