SOX4 reprograms fatty acid metabolism through the CHREBP to inhibit ferroptosis in hepatocellular carcinoma by Fan Zhang & Zhiwei Wu & Yang Xiang & Qing He & Wanqing Li & Kaipeng Yang & Yijun Yang instant download

SOX4 reprograms fatty acid metabolism through the CHREBP to inhibit ferroptosis in hepatocellular carcinoma by Fan Zhang & Zhiwei Wu & Yang Xiang & Qing He & Wanqing Li & Kaipeng Yang & Yijun Yang instant download

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by aggressive progression and poor prognosis.Pathological angiogenesis in HCC is closely linked to metabolic reprogramming, particularly concerning fatty acid metabolism. Theinterplay between fatty acid metabolism and ferroptosis, a type of cell death driven by lipid peroxidation, is emerging as a crucialarea of study. The transcription factor SOX4 is known to be overexpressed in various cancers, including HCC, and may play a keyrole in these processes. We assessed SOX4 expression in HCC using clinical samples and data from online databases. Nextgeneration RNA sequencing was employed to explore the effects of SOX4 on fatty acid metabolism, focusing on the CHREBPpathway. Functional assays, including lipid peroxidation and angiogenesis studies, were conducted to investigate the role of SOX4in regulating ferroptosis and angiogenesis in HCC. SOX4 was found to be significantly upregulated in HCC and associated with1234567890();,:enhanced angiogenesis. Mechanistically, SOX4 activated the CHREBP/SCD1 pathway, leading to increased production ofmonounsaturated fatty acids, which in turn inhibited ferroptosis. This suppression of ferroptosis contributed to the promotion ofangiogenesis and tumor progression in HCC. In conclusion, SOX4 reprograms fatty acid metabolism via the CHREBP/SCD1 pathway,thereby inhibiting ferroptosis and promoting angiogenesis in HCC. These findings suggest that targeting the SOX4-CHREBP axiscould represent a novel therapeutic strategy for HCC.Cell Death Discovery (2025) 11:246 ;