Fig. 4: VARS depletion re-sensitizes resistant melanoma cells to MAPK-based therapy.
From: Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma
a, Val-MAC-tRNA and Ile-RAT-tRNA aminoacylation activity of M395 RES cells depleted of VARS using two shRNAs (mean ± s.e.m. of n = 2 independent replicates). b–d, Cell death of patient-derived melanoma measured by fluorescence staining with PI by FACS of M395 RES (b), A375 RES (c) and a series of patient-derived melanoma cultures resistant to the drug combination BRAFi/MEKi (d). The cells were treated or not treated with vemurafenib (as indicated in b and c) or with dabrafenib/trametinib (as indicated in d) and depleted or not of VARS. e, As in b and c but with SENS cells overexpressing VARS. CTRL, control overexpression. f, A375 RES control or VARS-depleted melanoma cells were xenografted in mice and treated or not with vemurafenib (25 mg kg−1) (n = 10 for untreated and n = 11 for vemurafenib treated mice). Tumour weight mean ± s.e.m. was assessed and plotted. The mean ± s.e.m. of n = 3 independent replicates is indicated for b, c, d and e. A two-way analysis of variance was performed for b–f (P < 0.0001). Tukey’s multiple comparisons are indicated in the figures.
