Journal: Journal of Experimental & Clinical Cancer Research : CR
Article Title: Inflammatory interferon activates HIF-1α-mediated epithelial-to-mesenchymal transition via PI3K/AKT/mTOR pathway
Figure Lengend Snippet: 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-1 α mRNA transcription and translation as well as corresponding tumorigenic activities including EMT, anchorage-independent growth, invasion and vasculogenic mimicry activities. **, P
Article Snippet: Antibodies against fibronectin, vimentin, actin (Sigma), HIF-1α, HIF-1β, E-cadherin, N-cadherin, β-catenin, Bcl-2, MCL-1 (BD Bioscience), STAT1Y701 (Invitrogen), CA9, Glut1, PGK1, 4EBP1, MDR1, S6K, S6 and mTOR, Survivin (Genetex), IFN-alpha antibody (R & D systems, MN, USA), Bmi1 (Millipore Inc.) were obtained commercially.
Techniques: In Vitro, In Vivo, Expressing, Binding Assay, Activation Assay