Extended Data Fig. 5: Small-molecule inhibition of the methionine cycle disrupts the tumorigenicity of lung tumor-initiating cells.
From: Methionine is a metabolic dependency of tumor-initiating cells
a, Mean tumor mass of implanted cells. Error bars, s.d.; n = 6 (D9, DMSO), n = 9 (FIDAS, FIDAS + SAM) tumors. b, Left, mean percentage of CD166+ cells. Error bars, s.d.; n = 4 biologically independent experiments. Right, representative flow cytometry plots independently repeated four times. Unstained cells are in blue. c,d, Immunoblots of the indicated cells. β-catenin was used as a loading control. Independent blots were repeated at least three times with similar results. e, Proliferation curves generated from mean cell viability. Error bars, s.d.; n = 10 biologically independent experiments. f, Mean percentage of Annexin V+ cells. Error bars, s.d.; n = 4 (DMSO, D9), n = 3 (FIDAS) biologically independent experiments. g,h, Proliferation curves generated from mean cell viability. Error bars, s.d.; n = 10 biologically independent experiments. i, Mean tumor mass of implanted cells. Error bars, s.d.; n = 7 (control), n = 6 (FIDAS) and n = 9 (cisplatin) tumors. j, Mean number of GFP+ lesions. Error bars, s.d.; n = 5 lungs. ****P < 0.0001, two-sided unpaired Student’s t test. k, Individual weight plots of nine mice undergoing the indicated treatment. l, Mean MAT2A mRNA levels in normal versus tumor tissue, including glioblastoma (TCGA), colorectal cancer (TCGA), nasopharyngeal carcinoma81, leukemia82,83, lymphoma84, ovarian carcinoma85, melanoma86, prostate adenocarcinoma87 and breast cancer88. ****P < 0.0001, ***P < 0.001, **P ≤ 0.01, *P ≤ 0.05, Student’s unpaired two-sided t test with Welch’s correction. P values and numbers of normal and tumor samples are as follows: brain: P < 0.0001; n = 10 and n = 547; nasopharynx, P = 0.0005; n = 10 and n = 31; skin: P = 0.0015; n = 7 and n = 63; lymphatic system, P < 0.0001; n = 20 and n = 40; bone marrow (childhood acute lymphatic leukemia): P = 0.0492; n = 8 and n = 566; bone marrow (chronic lymphatic leukemia): P = 0.0003; n = 11 and n = 100; ovary: P < 0.0001; n = 10 and n = 185; breast, P = 0.0215; n = 5 and n = 59; prostate: P = 0.0010; n = 20 and n = 69; colon: P < 0.0001; n = 22 and n = 215. m, Immunoblots of the indicated cells. Independent blots were repeated at least three times with similar results.
