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Additional file 4: Figure S4. a Representative western blot results of HSP90 and HSP70 co-IP with 3xF-TRPM1. Cell lysates were prepared from Mel1617 cells stably expressing either an empty vector or 3xF-TRPM1 and IP with anti-FLAG M2 affinity gel. n = 3. b Quantification analysis, related to Fig. 4b, was performed for three independent experiments. Data are presented as the mean ± s.e.m. The P values were determined by two-tailed Student’s t-test, * P

Additional file 6: Figure S6. a Representative western blot results of ARPE19 (left) and A375 (right) cells expressing either scrambled shRNA or shRNAs specific for TRPM1. Quantification analysis was performed for three independent experiments. Data are presented as the mean ± s.e.m. The P values were determined by two-tailed Student’s t-test, * P

Additional file 7: Figure S7. A schematic representation of the mechanism of AUY922-induced retinal toxicity through attenuation of TRPM1.

Additional file 5: Figure S5. a Schematic representation of TRPM1 protein. b Quantification analysis, related to Fig. 5a, was performed for three independent experiments. Data are presented as the mean ± s.e.m, n = 3. c Representative western blot results of cells stably expressing either an empty vector or a vector encoding 3xFLAG-tagged wild-type TRPM1 (WT), TRPM1Ile1024Phe (I1024F) or TRPM1Cys1069Tyr(C1069Y). β-Actin was used as a loading control. Quantification was performed for three independent experiments. Data are presented as the mean ± s.e.m. n = 3. d Cytosolic Ca2+ levels were determined by flow cytometry and expressed as the MFI of the Ca2+ dye Fluo-8 AM in cells expressing either an empty vector or variants of TRPM1. Data are presented as the mean ± s.e.m. The P values were determined by two-tailed Student’s t-test, * P

Additional file 3: Figure S3. a Viability of A375 (blue line) and Mel1617 (red line) cells, after treatment with varying concentrations of AUY922 for 3 d. Data are presented as the mean ± s.e.m. (n = 3). b Representative images of clonogenic growth assays in Mel1617 (top) and A375 (bottom) cells treated with the indicated concentrations of AUY922 for 10 d. Three hundred cells/well were seeded in 6-well plates. n = 3. c Strategy for iTRAQ proteomic profiling of DMSO- and AUY922-treated 661 W cells. d Quantification of the AUY922 treatment experiments in 661 W, Mel1617 and A375 cells, related to Fig. 3d. Data are presented as the mean ± s.e.m. The P values were determined by two-tailed Student’s t-test, * P

Additional file 2: Figure S2. Representative images of H&E staining and TUNEL assays for REP flat mounts from the AUY922 treatment experiment in Fig. 1b. Scale bar: 25 μm. n = 3.

Additional file 1: Figure S1. a Full-field electroretinogram (ffERG) of a patient with refractory gastrointestinal stromal tumor without AUY922 treatment. OD: right eye, OS: left eye. b Quantification of tumor volume in nude mice bearing xenograft tumors of A375 cells treated with mock (n = 6), 25 mg/kg AUY922 three times weekly (3qw, n = 6), or five times weekly (5qw, n = 6) for 2 w by intraperitoneal injection. Data are presented as the mean ± s.e.m. The P values were determined by two-tailed Student’s t-test, *** P