1. MET inhibition promotes p21 nuclear translocation
MET inhibition promotes p21 nuclear translocation Western blot of BT371NS showing p21 phosphorylation (pp21Thr145) in cytoplasmic lysates immunoprecipitated with p21 antibodies at the indicated time points after IR in the absence (5 Gy) or in the presence (5 Gy + HGF) of HGF (10 ng/ml).Western blot of BT463NS showing p21 phosphorylation (pp21Thr145) in cytoplasmic lysates immunoprecipitated with p21 antibodies at the indicated time points after IR in the absence (5 Gy) or in the presence (5 Gy + JNJ) of the MET inhibitor JNJ (500 nM).Western blot of BT308NS showing p21 localization in cytoplasmic/nuclear extracts at the indicated time points after IR in the absence (5 Gy) or in the presence (5 Gy + JNJ) of JNJ Vinculin and lamin B were used as loading controls for cytoplasmic and nuclear fractions, respectively.Representative immunofluorescence staining of p21 (red) on BT308NS cells 3 h after IR (5 Gy) in the absence (vehicle) or in the presence (JNJ) of JNJ Ctrl: non‐irradiated cells. Nuclei are counterstained with DAPI (blue). Scale bar, 10 µm (63× magnification).Quantification of the percentage of cells showing p21 cytoplasmic or nuclear localization in BT308NS represented in (D) (n = 10 HPF/group). HPF: high‐power field. *: t‐test (5 Gy + JNJ) versus (ctrl or 5 Gy), P <  Cell cycle analysis of BT314NS, performed 24 h after IR in the absence (5 Gy) or in the presence (5 Gy + JNJ) of JNJ Vehicle: non‐irradiated cells. *: one‐way ANOVA, P =  n = 3.Schematic representation of the MET‐driven signaling pathways that sustain DNA repair and prevent apoptosis and cell cycle arrest.Data information: Data are represented as mean ± SEM.Source data are available online for this figure.
Francesca De Bacco et al. EMBO Mol Med. 2016;8:
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