Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms

Figure 1 Schematic review of the molecular mechanisms linking diabetes mellitus and colorectal cancer. Insulin and insulin-like growth factor (IGF-1) signaling pathways are shown, along with their effect on apoptosis, proliferation, and protein synthesis. The activated mitogen activated protein kinases (MAPK) pathway is associated with proliferation and the phosphatidyl-inositol-3-kinase (PI3K)/protein kinase B (Akt) pathway mainly leads to survival (inhibition of apoptosis). Moreover, protein synthesis is induced via the Akt pathway. The complexity of the system and the cross-talk between the individual pathways are presented. MEK: Mitogen extracellular kinases; ERK: Extracellular signal-regulated kinases; mTOR: Mammalian target of rapamycin; Ras: “Rapid accelerating sarcoma” serine/threonine-kinase; Raf: “Rapid accelerating fibrosarcoma” serine/threonine-kinase; Ryk: Related to tyrosine kinases; SOS: Silencing of survival signals; Grb2: Growth factor receptor binding protein 2; APC: Activated protein C; GSK-3β: Glycogen synthetase kinase-3β; Axin: Activated extracellular index.