Extended Data Fig. 1: The treatment response of sorafenib in MycOE;NrasG12V-driven HCCs is dependent on LXRα activation.
From: LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer
a,b, Treatment of murine, MycOE;NrasG12V-driven HCCs with sorafenib. Representative pictures (a) and H+E staining (b) of MycOE;NrasG12V HCCs in wildtype mice upon a 5-week therapy with sorafenib or the corresponding carrier (n = 3 mice per group). Scale bars, 1 cm, 100 µm. c, Survival of mice with MycOE;NrasG12V HCCs under sorafenib or carrier treatment (Kaplan-Meier curve, statistical significance was calculated using a log-rank test, n = 6 mice per group). d, Overview of LXRß structure with the coactivator peptide from NCOA1 (dark blue) in the AF2 region and sorafenib structure, docked in the ligand-binding pocket (orange). e, Suggested binding mode of sorafenib proposed by molecular modelling into the ligand-binding pocket of LXRß (PDB ID: 1PQ6). Residues contributing towards the interaction are colored by property, hydrophobic side chains are purple and hydrogen bonds are cyan. f, Schematic outline of an LXRα-binding saturation assay. Pulldown of LXRα was performed upon incubation with different concentrations of 3H-sorafenib. This experiment was side-by-side conducted in the presence of 320 µM unlabeled sorafenib to determine unspecific binding. g, Representative western blot analysis of LXRα in individual MycOE;NrasG12V;gN1h3 tumors (cropped blot images, MycOE;NrasG12V;gNC control: n = 3 mice, the western blot was repeated twice with similar results). α-tubulin was used as a loading control. Unprocessed images of the blots and numerical source data are provided as source data files.
