Highly Expressed Fatty Acid-Binding Protein 6 Mediates Lipid Metabolism Remodeling in Tumor Cells via Intracellular Bile Acid Transport to Promote Pancreatic Cancer Metastasis.

Pancreatic cancer (PC) endangers patients' lives and health, and the current diagnosis and treatment situation is not optimistic. Bile acids level was reported to be involved in PC progression, but how they regulate PC progression at the molecular level remains unclear. There is an urgent need to conduct in-depth research. Clinical samples from 58 PC patients and PC cells, including PANC-1 cells and CFAC-1 cells, served as the main research objects. RT-qPCR, IHC, and western blot were used to detect the levels of related molecules. Bile acids, lactate, triglycerides, and cholesterol levels were measured by commercial kits and the lipid levels were evaluated by Oil Red O assay. CCK-8, EdU, and Transwell assays were employed to detect malignant features of PC cells. In PC clinical samples, fatty acid-binding protein 6 (FABP6) expression and endogenous bile acid levels were abnormally elevated. Besides, FABP6 overexpression could accelerate tumor growth and metastasis and facilitated lipid metabolism reprogramming in PC mice. In addition, in PC cells, FABP6 overexpression promoted cellular lipid metabolism by enhancing intracellular bile acid transport, which promoted the malignant characteristics of PC cells. As expected, FABP6 silencing achieved opposite results. Moreover, FABP6 overexpression affected lipid metabolism reprogramming and promoted PC cell malignant features by strengthening intracellular bile acid transport to activate NR1H2/3. FABP6 overexpression promoted lipid metabolism reprogramming by enhancing intracellular bile acid transport to activate NR1H2/3, thereby accelerating PC progression. These findings offered new insights into PC molecular mechanisms and potential therapeutic targets.