DLAT is involved in ovarian cancer progression by modulating lipid metabolism through the JAK2/STAT5A/SREBP1 signaling pathway

作者：Hui Wang, Shen Luo, Yue Yin, Yan Liu, Xiaomei Sun, Ling Qiu, Xin Wu · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03656-7 · 被引用次数：6 · 研究领域：Cancer, Lipids, and Metabolism、Ferroptosis and cancer prognosis、Cholesterol and Lipid Metabolism

BACKGROUND: Ovarian cancer (OC) remains a lethal gynecological malignancy with an alarming mortality rate, primarily attributed to delayed diagnosis and a lack of effective treatment modalities. Accumulated evidence highlights the pivotal role of reprogrammed lipid metabolism in fueling OC progression, however, the intricate underlying molecular mechanisms are not fully elucidated. METHODS: DLAT expression was assessed in OC tissues and cell lines by immunohistochemistry, western blot and qRT-PCR analysis. The effects of DLAT silencing on changes in lipid metabolism, cell viability, migration, and invasion were examined in SKOV3 and OVCAR3 cells using CCK-8, colony formation, Transwell migration and invasion, and wound-healing assays. GSEA analysis was used to examine the relationship between DLAT and lipid metabolism-related enzymes. Rescue experiments in which SREBP1 was overexpressed in DLAT-silenced cells were carried out. Western blot analysis was performed to determine whether the JAK2/STAT5 signaling pathway was involved in DLAT-regulated SREBP1 expression. Commercially available triglyceride and cholesterol detection kits, as well as Nile Red and Oil red O staining were used to measure lipid metabolism. A subcutaneous tumor model was established in BALB/c mice to confirm the role of the DLAT/SREBP1 axis in OC growth and metastasis in vivo. RESULTS: DLAT expression was significantly upregulated in OC patient tissue and associated with poor prognosis. Silencing DLAT red...