In conclusion, our report indicates that increased autophagy may be an important mechanism to enable p53-deficient or mutant p53-expressing colon cancer cells to acquire resistance to 5-FU, and JNK activation triggers autophagy as a pro-survival effect to protect cancer cells against the cytotoxic effects of 5-FU, probably via inducing Bcl-2 phosphorylation. Here, MAPK8 is linked to malignant colon neoplasm.