Extended Data Fig. 7: Melanoma cells that are resistant to BRAF-inhibitors show increased levels of U34 enzymes and high HIF1α-dependent metabolism.
From: Codon-specific translation reprogramming promotes resistance to targeted therapy
a, Indicated mRNA levels of isogenic primary melanoma cells sensitive (SENS) or resistant (RES) to vemurafenib (1 μM) were assessed by qPCR. n = 2 independent experiments, data are mean + s.d. b, Indicated mRNA levels of HIF1α targets of cells in a were assessed by qPCR. n = 2 independent experiments, data are mean + s.d. c, Cells as in a. Lactate production in the medium was quantified by NMR. n = 3 independent experiments, two-sided t-test, data are mean + s.d. d, Lactate production in the medium was assessed in cells as in a after 24 h by luminescence assay. n = 2 independent experiments, data are mean + s.d. e, f, Melanoma cell lines, which differ in BRAF status and in sensitivity to MAPK inhibitors (MeWo is BRAFWT, insensitive; SkMel5 is BRAFV600E, sensitive; A2058 is BRAFV600E, resistant) were depleted of ELP3 by shRNA and treated for 24 h with the indicated concentrations of vemurafenib or the U0126 MEK1 inhibitor (top and bottom panels of e, respectively). e, Cell death was quantified by FACS. n = 9 independent experiments, two-sided t-test, data are mean ± s.d. f, Synergy between specific inhibitors and ELP3 depletion was calculated by the Calcusyn software. C.I. index, in red the synergistic C.I. value. g, h, As in e and f, but with cells depleted of CTU2. n = 9 independent experiments, two-sided t-test, data are mean ± s.d.
