Fig. 6

Regulation of c-Myc by the FGF/FGFR system in cancer. Activation of the FGFR signaling regulate c-Myc activity at both transcriptional and post-translational level. A FGFR phosphorylation activates transcription factors such as ERK1/2 and STAT3 that promote MYC transcription. Also, FGFR1 fusion kinase in the cytoplasm can activate STAT5 that contributes to MYC transcription. Alternatively, the truncated form of the FGFR1 fusion kinase generated from the cleavage by granzyme B can translocate to the nucleus where it recognises specific binding sites in the MYC locus having a direct effect on MYC expression. B FGFR phosphorylation activates the kinase activity of ERK1/2 that in turn leads to c-Myc S62 phosphorylation and c-Myc stabilization. At the same time, FGFR also triggers PI3K/AKT pathway that inhibits GSK-3β kinase, thus preventing c-Myc T58 phosphorylation and c-Myc proteasomal degradation