Extended Data Figure 10: The apoptotic response profile of a panel of cancer cells following HSP90 inhibition is independent of levels of chaperome members, HSP90 client proteins and anti-apoptotic molecules, tissue of origin or causal genetic mutations.
From: The epichaperome is an integrated chaperome network that facilitates tumour survival
a, Total levels of the indicated chaperome members, HSP90 client proteins and anti-apoptotic molecules were analysed by western blot in a panel of pancreatic cancer cells (n = 12). GAPDH and β-actin, protein loading controls. Protein levels were quantified and graphed against the viability of these cells upon HSP90 inhibition. A correlative analysis was performed (Pearson’s r, two-tailed). Each data point represents a cell line. PU-FITC binding is shown for comparison. b, Correlative analysis of epichaperome abundance, as measured by PU-FITC staining, and cell viability upon a 48 h treatment with PU-H71 (1 μM), as measured by annexin V staining (Pearson’s r, two-tailed). Each data point represents a cell line (n = 95); data are the mean from two orthree biological replicates. Cells representing pancreatic, gastric, lung, and breast cancers, along with lymphomas and leukaemias were chosen for analysis. c, Same as above for the treatment of cancer cells (n = 12) with three chemically distinct HSP90 inhibitors. d, Same as b, but for each cell line, known genetic lesions were added. No specific genetic alteration could be found distinguishing the two tumour types; whereas p53-, Ras-, Myc-, HER-, PI3K/AKT-, and JAK- cell cycle-related defects were found in tumours that were sensitive to PU-H71, they were also evident in PU-H71 resistant cells. We found genetic defects in major chaperome members to be rare, with BCP-1 cells only carrying an HSP90AA1 missense mutation (P596S). No mutations in HSP90AB1, HSPH1, HSPA8, STIP1 and AHSA1 were reported in this large panel of cell lines. These were obtained from the cBioPortal for Cancer Genomics website (http://www.cbioportal.org/).
