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. Author manuscript; available in PMC: 2019 Dec 1.
Published in final edited form as: Clin Cancer Res. 2018 Aug 2;24(23):5963–5976. doi: 10.1158/1078-0432.CCR-18-0876

Figure 5.

Figure 5.

Model of resistance to MET and MET/MAPK/ERK inhibition in DFCI358. A, At baseline, mutant MET in parental DFCI358 cells activates KRAS, which in turn amplifies downstream MAPK/ERK signaling resulting in enhanced transcription and release of EGFR ligands. B, Upon MET inhibition in parental DFCI358 cells, amplified KRAS sustains MAPK/ERK signaling via EGFR-ligand stimulated EGFR and other activated RTKs. C, Upon dual MET/MEK inhibition in KRAS amplified NS Control DFCI358 cells, cell viability is sustained by the PI3K/AKT pathway activated directly by amplified KRAS. D, With KRAS downregulation and MET inhibition in KRAS KD DFCI358 cells, resulting in diminished MAPK/ERK signaling, cell viability is sustained by the PI3K/AKT pathway activated by RTKs, such as IR/IGF1R, HER2 and EGFR.