Fig. 8: Genetic inactivation of UHMK1 sensitizes BRAFV600 melanoma cells to BRAF and MEK combination therapy in vitro and in vivo.
a Cell proliferation was assessed by monitoring confluency over time using an Incucyte automated microscope in melanoma cells transfected with the indicated siRNA and treated with DMSO, 300 nM Vem, 10 nM Cobi or Vem + Cobi. Proliferation curves representative of n = 3 biologically independent experiments are shown. Data represent mean confluency ± StDev. b Average % confluency normalized to T0 following 96 hr treatment as described in (a). Data represent mean ± SEM of n = 3 biologically independent experiments. c Schematic of the in vivo drug sensitivity study. d UHMK1 was genetically inactivated in A375 cells using CRISPR-Cas9 and UHMK1 KO was confirmed using RT-qPCR (top panel) and western blot analysis of UHMK1 target p27 (bottom panel). e Growth of A375-CAS9, A375-UHMK1-gRNA2 and A375-UHMK1-gRNA4 tumours treated with vehicle or dabrafenib and trametinib (Dab/Tram). Data represent mean tumour growth ± SEM of n = 9 individual mice per group. f Kaplan–Meier curve of data in (e) shows survival advantage where survival is defined as time to a tumor exceeding a volume of 1200 mm3. Statistical significance was determined by Log-rank (Mantel-Cox) test. g Cell proliferation was assessed in NRAS mutant melanoma cells (IPC298 and D04M1) transfected with the indicated siRNA and treated with DMSO or 1 nM trametinib (tram) by monitoring confluency over time using an Incucyte automated microscope. Proliferation curves representative of n = 3 biologically independent experiments are shown. Data represent mean ± StDev. Source data are provided as a Source Data file.
