Rong, X. et al. ER phospholipid composition modulates lipogenesis during feeding and in obesity. J. Clin. Invest. 127, 3640–3651 (2017). Chen, K. F. et al. Activation of phosphatidylinositol 3-kinase/Akt signaling pathway mediates acquired resistance to sorafenib in hepatocellular carcinoma cells. J. Pharmacol. Exp. Ther. 337, 155–161 (2011). a, Quantification of western blot analysis (shown in Fig. 6b) to quantify relative SCD1 expression in Myc OE; Nras G12V; Cdkn2a ARF–/– cells upon 3 days of treatment with sorafenib, T0901317 or a combination thereof (quantified with ImageJ, only samples from the same blot were compared, values represent mean ± SD, n = 6 independent experiments, statistical significance was calculated using two-tailed Student´s t test, α-tubulin was used as a loading control). b, Quantification of western blot analysis (shown in Fig. 6c) to quantify relative SCD1 expression in Myc OE; Nras G12V; Cdkn2a ARF–/– cells upon treatment with T0901317 (2 d) and sorafenib (1-3 h) (quantified with ImageJ, only samples from the same blot were compared, values represent mean ± SD, n = 6 independent experiments, statistical significance was calculated using two-tailed Student´s t test, α-tubulin was used as a loading control). c, Representative western blot analysis of SCD1 in HLE cells upon treatment with T0901317 (2 d) and sorafenib (1-3 h) (cropped blot images, n = 3 independent experiments). α-tubulin was used as a loading control . d-f, Representative western blot analysis of SCD1 in Myc OE; Nras G12V; Cdkn2a ARF–/– cells upon treatment with T0901317 (2 d) and the DFG-out RAF inhibitors RAF-265 ( d) and RAF-709 ( e) or the DFG-in DFG-in RAF inhibitor SB590885 ( f) for 1 to 3 h (cropped blot images, n = 2 independent experiments). α-tubulin was used as a loading control. g, Representative western blot analysis of MEK and p-MEK1/2 (Ser217/221) in Myc OE; Nras G12V; Cdkn2a ARF–/– cells upon 6 h of treatment with sorafenib, BI-882370, dabrafenib or SB590885 (cropped blot images, n = 2 independent experiments). α-tubulin was used as a loading control. h, Representative western blot analysis of SCD1 in Myc OE; Nras G12V; Cdkn2a ARF–/–; Raf1 WT cells upon treatment with T0901317 (2 d) and sorafenib for 1 to 3 h (cropped blot images, n = 2 independent experiments). α-tubulin was used as a loading control. i, Representative western blot analysis of Raf-1 in Myc OE; Nras G12V; Cdkn2a ARF–/–;sh Raf1 or Myc OE; Nras G12V; Cdkn2a ARF–/–;shNC cells, 4 days upon treatment with doxycycline (cropped blot images, n = 2 independent experiments). j, Treatment of Myc OE; Nras G12V; Cdkn2a ARF–/– cells with carrier, T0901317, the MEK1/2 inhibitor PD0325901 or a combination thereof (quantification of viable cells by crystal violet staining, values represent mean ± SD, n = 3 independent experiments, statistical significance was calculated using two-tailed Student´s t test). Unprocessed images of the blots and numerical source data are provided as source data files.

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