fig2

Figure 2. Direct effects of APN on epithelial ells and summary of APNs anti-cancer signalling 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). Green arrows represent activating pathways. Red lines represent inhibitory pathways. gAcrp: globular adiponectin; flAcrp: full length adiponectin; RTK: receptor tyrosine kinase; JAK: Janus kinases; Stat: signal transducer and activator of transcription proteins; PI3K: PI3-kinases; Akt: protein kinase B; mTOR: mammalian target of rapamycin; AMPK: 5’ APM activated protein kinase; GSK3β: glycogen synthase kinase-3 beta