Fig. 4

Co-localization of signaling molecules in the nucleus. a Western blot analysis of the anti-Src antibody co-immunoprecipitate in the nuclear fractions of the three HCC cell lines. Src co-immunoprecipitated with STAT3, but not with FGFR4. b Immunofluorescence staining of FGFR4, pSrc, and pSTAT3 in SNU878 cells. FGFR4 and pSTAT3 were co-localized in the cytosol, but not in the nucleus. pSrc and pSTAT3 were co-localized in the cytosol and nucleus. c Schematic model depicting the endosomal delivery of the FGFR4 signaling complex. FGF19 activates FGFR4, which forms an endosomal complex with pSTAT3 and pSrc, and is transported to the nucleus. d Effects of dasatinib on Src phosphorylation. The level of Src phosphorylation decreased with dasatinib treatment. e–h Viability of HCC cells treated with the Src inhibitor, dasatinib, or with the FGFR4 inhibitor BLU9931 (**P < 0.0001). The cytotoxic efficacy of dasatinib was comparable to that of BLU9931