Fig. 1.
Model for APN-mediated suppression of cancer promoting pathways. In normal epithelial cells, APN is bound by T-cadherin and presented directly or indirectly to AdipoR1/R2 to inhibit signaling pathways activated in neoplasia. APN-activates AMPK, and inhibits PI3K/AKT, mTOR, MAPK and JAK/Stat pathways, or directly affects GSK3β to suppress cancer promoting pathways. Cancer cells down-regulate T-cadherin while AdipoR1/R2 expression persists and cancer promoting pathways prevail. One model is that ceramidase activity associated with AdipoR1/R2 weighs the balance in favor of cancer cell survival. T-cadherin expressed in the tumor vasculature promotes cancer as a pro-angiogenic factor in cooperation with APN (not shown [38,39]). Black arrows, activating pathways; red lines with bar: inhibitory pathways.