MAPK3 and malignant colon neoplasm: Since in colon cancer metformin exerts an anti-proliferative effect by suppressing IGF-1R signaling [10], we next analyzed the activating phosphorylation pattern for Akt and extracellular signal-regulated kinases 1/2 (ERK1/2), the two main IGF-1R downstream pathways in H295R cells [11].