Fig. 6: TET2 deficiency sensitizes tumor cells to mTORC1 inhibition.

a TET2 KO-induced growth advantage was reversed by rapamycin treatment. Cells were treated with 10 nM rapamycin as indicated. n = 3 biologically independent samples per group. b TET2 KO-promoted colony formation was reversed by rapamycin treatment. Cells were treated with 10 nM rapamycin. n = 3 biologically independent samples per group. c A total of 371 LIHC tumors from TCGA database were divided into two groups based on TET2 mRNA levels (top and bottom 50% TET2 expression), and their relative mTORC1 activities were qualified and plotted as described in Materials and methods. d, e TET2 and EGFR mutations, as well as PTEN-EGFR mutations, are mutually exclusive, respectively, in NSCLC (d). Mutations in IDH1/2-TET2 axis and mTORC1 signaling (including PTEN and EGFR mutations alone, respectively, and PTEN-EGFR mutations) display mutual exclusivity in LGG and GBM (e). Each vertical lane represents one patient, while green lines indicate the presence of mutations. Statistical analysis was performed using the Fisher’s exact test. f, g TET2 deficiency sensitizes tumor cells to rapamycin treatment in vitro. WT and TET2 KO tumor cells were treated with 100 nM rapamycin for varying days as indicated (f), or different concentrations of rapamycin as indicated for 6 days (g). n = 4 biologically independent samples per group. h TET2 deficiency sensitizes tumor cells to rapamycin treatment in vivo. WT and TET2 KO HepG2 cells were subcutaneously injected into the left flanks of athymic nude mice. Tumor inhibition rate of rapamycin was measured and calculated every other day as indicated. n = 6 biologically independent animals per group. i IHC analyses of tumors from nude mice were performed with indicated antibodies. Scale bar, 20 μm. n = 3 biologically independent animals per group. j Western blot analyses of tumors from nude mice were performed with indicated antibodies. n = 2 biologically independent animals per group.