Supplementary Figure S1-S6 from ERK Mutations and Amplification Confer Resistance to ERK-Inhibitor Therapy

Fig. S1. ERK inhibitors and their effect on MAPK mutant cell lines. A. Structure of ERK inhibitors used in this study. B. Dose response curve of ERK inhibitors on the viability of A375, IPC298, SKMEL30, HCT116, MIA PaCa2 and Panc1 cells. Fig. S2. Western blot analysis of parental, VI-3-R and G994-R HCT116 (A) or MIA PaCa2 (B) cells treated with indicated ERK inhibitors. Fig. S3. Western blot analysis of HCT116 cells (A) and SKMEL30 (B) stably expressing indicated ERK1 or ERK2 mutants. Fig. S4. Copy number and expression analysis of MITF in SKMEL30-ERKi-R cells. A. MITF copy gain in SKMEL30-V11e-R, -VI-3-R and -G994-R. B. MITF copy number vs. expression in SKMEL30-V11e-R, VI-3-R and G994-R cells. Fig. S5. Dose response curve of ERK2 overexpressing IPC298 cells treated with MEK inhibitors GDC-0973 or AZD6244 (A) and ERK2 amplified IPC298-G994-R (B) or MIA PaCa2-S984-R (C) cells treated with indicated ERK-inhibitors from alternate scaffold class. Fig. S6. Dose response curve of parental or ERKi-resistant HCT116 (A) and MIA PaCa2 (B) cells treated with indicated inhibitors. The data shown are same as in Fig. 6B for HCT116 (A) and Fig. 6C for MIA PaCa2 (B) grouped by drug treatment.