Strikingly, in accordance with p38 MAPK involvement in many different cellular processes, it appears that MKK3 contribution to CRC tumor growth is manifold: in fact, we observed a cancer cell-line-specific dependence on MKK3, with autophagy being induced only in a subset of CRC lines upon MKK3 depletion, while this caused potentiation of 5-FU-induced killing in all of the tested CRC lines indicating that MKK3 inhibition exerts tumor-suppressive effects also by affecting mechanisms other than autophagy induction. The gene discussed is MAP2K3; the disease is cancer.