1. Supplementary Figure 1. The effect of 17-DMAG on the growth of lung cancer cells with Met amplification Tumor cells were continuously treated with increasing concentrations of EGFR-TKI, erlotinib, or 17-DMAG, with or without HGF (20 ng/ml), and cell growth was determined after 72 hours by MTT assay. Data shown are the representative of 3 independent experiments. Error bars indicate SD of triplicate cultures. % cell viability Drug concentration (μM) HCC827ER HGF(+) % cell viability Drug concentration (μM) HCC827ER HGF(-)

2. Drug concentration (μM) % cell viability PC-9 HGF(+) Ma-1/HGF % cell viability Drug concentration (μM) % cell viability H1975 HGF(+) Drug concentration (μM) % cell viability PC-9 HGF(-) Drug concentration (μM) % cell viability H1975 HGF(-) Supplementary Figure 2. The effect of combined therapy with 17-DMAG and EGFR- TKI on the growth of lung cancer cells with mutated EGFR Tumor cells were continuously treated with increasing concentrations of EGFR-TKI, erlotinib (PC-9 and Ma-1/HGF), CL-387,785 (H1975), or 17-DMAG, with or without HGF (20 ng/ml), and cell growth was determined after 72 hours by MTT assay. Data shown are the representative of 3 independent experiments. Error bars indicate SD of triplicate cultures.

3. Supplementary Figure 3. < 0.1 HGF (ng/ 2×10 5 cells)

4. AnnexinV 2.9031.5235.493.055.4424.89 1.6414.0112.110.69 2.85 15.64 2.644.0417.81 PI ControlErlotinib17-DMAGHGFHGF+ErlotinibHGF+17-DMAG Ma-1 Ma-1/Vec Ma-1/HGF Supplementary Figure 4. 17-DMAG induces apoptosis even in the presence of HGF. Ma-1, Ma-1/Vec, and Ma-1/HGF cells were incubated with HGF (20 ng/mL) and erlotinib (0.3 μmol/L) or 17-DMAG (0.3 μmol/L) for 48 hour and washed twice with PBS. The apoptotic cells were determined by Annexin V assays according to the manufactor’s protocol. Values shown are percentage of apoptotic cells. FL1-H and FL2-H, heights of fluorescence intensity.

5. Supplementary Figure 5. The effect of combination treatment with 17-DMAG plus erlotinib to HGF-induced erlotinib resistance in vivo. Ma-1 /Vec (A) or Ma-1/HGF (B) (5 × 10 6 ) cells were inoculated subcutaneously into SCID mice on day 0. Mice received oral erlotinib (20 mg/kg/d) and/or intraperitoneal 17-DMAG (10 mg/kg/d), starting on day 7. Tumor size was measured twice a week and tumor volumes were calculated as described in Materials and Methods. Error bars indicate standard errors of 6tumors. C, macroscopic appearances of representative tumors harvested on day 21. 1 2 3 4 5 6 7 8 1: Ma-1 Control 2: Ma-1 Erlotinib 3: Ma-1 17-DMAG 4: Ma-1 Combination 5: Ma-1/HGF Control 6: Ma-1/HGF Erlotinib 7: Ma-1/HGF 17-DMAG 8: Ma-1/HGF Combination C A B

6. Ma-1/Vec Ma-1/HGF ControlErlotinib17-DMAG Supplementary Figure 6.

7. ControlErlotinib17-DMAG Ma-1/Vec Ma-1/HGF Supplementary Figure 7.