Fig. 7.

The PI3K/AKT/mTOR signaling axis and HIF-1α play roles in cellular growth, invasion, vasculogenic mimicry, sphere formation activities in vitro and tumor growth in vivo induced by acute IFN-α exposure. a-c Pharmacological inhibitions of the JAK/PI3K/PTEN/mTOR/AKT, Ras/p38/MEK/ERK axes and HIF-1α significantly impacted on the IFN-α-stimulated anchorage-independent growth (a), scratch wound closure (b) and vasculogenic mimicry formation (c) in 769-P cells. d Inhibitors (as indicated) differentially affected expression of genes involved in EMT, cell survival and apoptotic cell death. e-f HIF-1α is needed for sphere colony formation (e), tumor formation and growth (f) of differentially educated 769-P cells; i.e. pSuper, pSuper + IFN, pshHIF-1α and pshHIF-1α + IFN cells. g Schematic illustration of the signaling pathways involved in the IFN-α-induced HIF-1α expression and stimulated tumorigenic propensities. The IFN-α-induced H IF-1α expression by first binding to the interferon alpha receptor 1 and 2 (IFNAR1/2), subsequent activation of JAK1 and TYK2, phosphorylation of PI3K, AKT and mTOR, those lead to promotion of HIF-1α mRNA transcription and translation as well as corresponding tumorigenic activities including EMT, anchorage-independent growth, invasion and vasculogenic mimicry activities. **, P < 0.01; ***, P < 0.001