Journal: Cell Death & Disease

Article Title: MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing

doi: 10.1038/s41419-024-06775-7

Figure Lengend Snippet: A The superimposed MAL2 protein (AlphaFold ID: AF-Q969L2-F1) alongside compounds chosen via computer-aided screening. B Conformational and docking advantages of sarizotan from the leading MAL2-compound scoring top-five interaction model. C A simplified depiction of sarizotan occupying the MAL2 protein’s active site. D MST analysis quantified the binding tenacity between sarizotan and MAL2. E The impact of sarizotan on the EGFR/PI3K/AKT signal pathway in HUCCT1 and RBE cells was explored using western blotting. F CCK-8 assay traced the growth trajectories of HUCCT1 and RBE cells under DMSO or sarizotan administration at 0, 24, 48, and 72 h intervals. G Cell propagation of ICC cells under DMSO or sarizotan treatment was scrutinized via EdU assay, scale bar, 50 μm. H Representative images of tumors from nude mice treated with DMSO or sarizotan. I , J Tumor growth curves and tumor weights of each group. K The expression level of Ki67 in nude mice-derived xenograft tumor was determined by IHC, scale bar, 50 μm. *** P < 0.001.

Article Snippet: Fatostatin (SREBP-1 inhibitor), EGF, CHX, AG1478 (EGFR inhibitor), Sarizotan, and PA were bought from MedChemExpress, China.

Techniques: Binding Assay, Western Blot, CCK-8 Assay, EdU Assay, Expressing, Derivative Assay

Journal: Cell Death & Disease

Article Title: MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing

doi: 10.1038/s41419-024-06775-7

Figure Lengend Snippet: When EGF is instigated, MAL2 sustains the membrane presence of EGFR, averting endocytosis, and persistently triggers the PI3K/AKT/SREBP-1 route. This sequence of events consequently accelerates lipid accretion in ICC and induces cisplatin insensitivity. Increased PA succeeds in preserving the membrane localization of MAL2. Sarizotan is identified as a diminutive molecular disruptor of MAL2, signifying its prospective utility in ICC therapy.

Article Snippet: Fatostatin (SREBP-1 inhibitor), EGF, CHX, AG1478 (EGFR inhibitor), Sarizotan, and PA were bought from MedChemExpress, China.

Techniques: Membrane, Sequencing, Preserving