Targeting cMET in parental MiaPaCa2 (MiaPaCa2(par)) and resistant MiaPaCa2 (MiaPaCa2(G250)) pancreatic cancer cell lines. A) In MiaPaCa2(G250) cells, cMET expression was detectable whereas no cMET was found in MiaPaCa2(par). B) MiaPaCa2(par) showed little response to cMET inhibition with INC280 even when cells were stimulated with HGF (50 ng/ml). C) Growth of MiaPaCa2(G250) was significantly improved when cells were incubated with HGF (#P < 0.05). cMET inhibition with INC280 inhibited this growth induction (*P < 0.05). D) Migration of MiaPaCa2(par) was increased when cells were stimulated with HGF (not significant); cMET inhibition did not affect constitutive or HGF-induced motility in these cells. E) In MiaPaCa2(G250) stimulation with HGF led to a significant increase in cancer cell motility (#P < 0.05), which was abrogated by targeting cMET with INC280 (*P < 0.05). F) In MiaPaCa2(par) stimulation with HGF led to weak induction of Akt and ERK phosphorylation. This was diminished by treatment with INC280. No effects on constitutive signaling were observed. G) HGF showed strong induction of Akt, ERK and FAK phosphorylation in MiaPaCa2(G250). Targeting cMET impairs effects on HGF-induced activation of signaling intermediates. H) Mimicking hypoxic conditions with DFX (100 μM) significantly induced MDR-1 mRNA expression in MiaPaCa2(G250) (#P < 0.05) and cMET inhibition with INC280 abrogated this (*P < 0.05). MDR-1 mRNA was not detectable in MiaPaCa2(par). Bars = SEM I) INC280 impairs DFX induced HIF-1α expression in MiaPaCa2(G250) cells.