As an important mitogen, insulin may promote cancer progression through its binding to the insulin receptor (IR) and/or IGF-1R (insulin-like growth factor receptor), which results in auto-phosphorylation of insulin-receptor substrate-1 (IRS-1) and activation of the phosphatidylinositol 3-kinase (PI3K)/Akt (serine/threonine kinase)/mammalian target of rapamycin (mTOR) pathway and the mitogen-activated protein kinase (MAPK) pathway36. Here, IRS1 is linked to cancer.