Extended Data Fig. 12: Taurine activates mTOR to promote leukaemia growth.
From: Taurine from tumour niche drives glycolysis to promote leukaemogenesis
a,b, Immunoblot and quantification of mTOR pathway proteins in +/+ Lin− bcCML treated with indicated doses of TAG (a, mean ± s.d.; n = 2 replicates per cohort) or 1 mM GES (b, mean ± s.e.m.; n = 4 samples per cohort). c-f, Experimental strategy (c), immunoblot (d, f), and quantification (e) of indicated proteins in Lin− bcCML cells +/− 200 mM taurine (mean ± s.e.m.; n = 3 biological replicates; gels processed in parallel; tubulin run on each gel as sample processing control). g,h, Immunoblots (g), and quantification (h) of mTOR pathway proteins in Lin− bcCML cells from leukaemic mice supplemented with taurine for 10 days (mean ± s.e.m.; n = 4 control and n = 5 taurine; b, e, h unpaired two-tailed Student’s t-test). i, Survival curve shows impact of 5 mg/kg rapamycin treatment for 6 d on leukaemia progression. Line represents treatment days (n = 9 +/+ and n = 5 −/−; data combined from two independent experiments; log-rank test). j, Histogram and geometric Mean Fluorescence Intensity (MFI) of p-mTOR in Lin− bcCML cells treated with DMSO or N-Oleoyl taurine for 36–40 h. (mean ± s.e.m.; n = 4 samples per cohort; data combined from two independent experiments). k,l, Expression of glycolysis genes in +/+ Lin− bcCML cells treated with rapamycin for 24 h (k; mean ± s.d.; n = 3 technical replicates per cohort) or 2 mM MHY1485 for 48 h (l; mean ± s.e.m.; n = 3 technical replicates per cohort; data combined from two independent experiments). m, Histogram and MFI of p-mTOR in Lin− bcCML cells infected with vector or RagA(Q66L) (mean ± s.e.m.; n = 6 samples per cohort; data combined from two independent experiments). n, CFU of Lin− bcCML cells infected with vector or RagAQ66L and treated with indicated amounts of taurine (mean ± s.e.m.; n = 3 independent culture wells per cohort; data combined from two independent experiments; j, l-n one-way ANOVA). o, Schematic shows taurine from BM osteolineage cells promotes RagA-dependent mTOR activation and glycolysis in leukaemia cells to drive disease progression. The culture well image in c is adapted from ref. 6, Springer Nature America.
