Fig. 1. Protein and mRNA expression of MET and ERBB family RTKs in CMM.

a Kaplan–Meier analysis of TCGA dataset relating changes in mRNA of MET and ERBB family members to OS in CMM alone or together (n = 461). b Images showing membranous and cytoplasmic protein expression of MET and ERBB3 in CMM. c Kaplan–Meier analysis showing effects of high or low MET protein expression on OS in CMM patients (n = 15) (Log-rank (Mantel–Cox) test). d AmpliSEQ data comparing PFS (<6 months or >6 months) after MAPK targeting treatment with relative mRNA expression of known afatinib and crizotinib targets in pre-treatment clinical samples (n = 13). e Relative mRNA expression in MET and ERBB family RTKs in matched metastases taken before the start of treatment with vemurafenib and after progression from two CMM patients. f Western blotting showing that knockdown of MET leads to the upregulation of EGFR, IGF1R, pAKT, and total AKT expression in vemurafenib-resistant subline A375VR4, which is blocked by co-silencing MET and EGFR. g Quantification of Fig. 1f using ImageJ. h Western blottings showing that afatinib targets p-ERBB3 and crizotinib targets pMET. *ND = Not detected. All samples are expressed as mean ± SD. All experiments were repeated in triplicates. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 as determined by two-tailed Student’s t-test