TAL1 Suppresses High-Grade Serous Ovarian Cancer Progression by Transcriptionally Inhibiting TPI1-Mediated Glycolysis

High-grade serous ovarian cancer (HGSOC) is often accompanied by a poor prognosis, which urges the development of new therapeutic approaches. This study attempts to explore the role of T-cell acute lymphocytic leukemia Protein 1 (TAL1)-triosephosphate isomerase 1 (TPI1) mechanism in glycolysis-driven progression of HGSOC. Bioinformatics analysis identified TPI1 as upregulated in HGSOC tissues. This was confirmed by RT-qPCR and Western blotting (WB) in HGSOC cells. Functional assays, including EdU, colony formation, and Transwell, showed that TPI1 knockdown or knockout suppressed HGSOC cell proliferation, migration, invasion, and glycolysis. TAL1 was found to be downregulated in HGSOC cells, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed that TAL1 directly repressed TPI1 transcription by binding to its promoter. Importantly, overexpression of TAL1 suppressed HGSOC progression and glycolysis, whereas combined overexpression of TPI1 rescued these effects. Blocking glycolysis attenuates the effect of TPI1 overexpression on malignant proliferation and metastatic-like behavior in HGSOC cells. These findings demonstrate that TAL1 inhibits HGSOC progression by blocking glycolysis through transcriptional repression of TPI1, suggesting a potential therapeutic target for intervention in HGSOC.