These results thus demonstrate that downregulation of Sam68 lessens colon tumor development in Apcmin716/+ mice and sensitizes human colon cancer cells to genotoxic stress-induced apoptosis, in line with the indispensible role of Sam68 in the nuclear-initiated PARylation, NF-κB activation, and anti-apoptotic transcription in mouse and human colon cancer cells. The gene discussed is NFKB1; the disease is colonic neoplasm.