Methylstat activates the UPR pathway in PTEN-deficient TNBC cells. (A) Venn diagram showing up- and down-regulated genes (>1.5 fold, P ≤ 0.05) by Methylstat (2.5 µM) for 24 h in PTEN-deficient MB468 and HCC70 and PTEN wild-type MB231 cells (left panel). Heat map is showing common Methylstat-responsive genes in PTEN-deficient MB468 and HCC70 (right panel). (B) IPA showing nine hallmark pathways exhibiting enrichment of Methylstat-responsive genes in MB468 and HCC70. Graph displays category scores as –log10 (P value) from Fisher’s exact test. TOB, transducer of ErbB2. (C) Western blot analysis of the UPR pathway in indicated TNBC cell lines treated with 2.5 µM Methylstat for 24 h. MW, molecular weight. (D) Western blot analysis of the UPR pathway in response to indicated concentrations of Methylstat for 24 h. (E) Western blot analysis of UPR in cells treated with 2.5 µM Methylstat for indicated hours. (F) Western blot analysis of UPR in indicated TNBC cells treated with 5 µM ML324 for 24 h. See also Fig. S1 and Tables S1 and S2. All data are representative of three independent experiments.