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The MYBL2-GTSE1 axis promotes laryngeal squamous cell carcinoma progression by regulating PI3K/AKT-dependent glycolytic reprogramming

Year: 2026

Type: article

Abstract: Background Laryngeal squamous cell carcinoma (LSCC) is a common head and neck malignancy with poor prognosis. The role of MYBL2, an oncogenic transcription factor, in the glycolytic reprogramming of LSCC remains unclear.Methods We integrated RNA-sequencing with public databases (TCGA, GEO) and tissue microarrays to assess MYBL2 expression and its clinical significance. Transcriptional regulation was verified by ChIP-qPCR and luciferase reporter assays. Signaling pathways and metabolic profiles were examined using Western blotting and Seahorse analysis (ECAR/OCR). Biological functions were evaluated by in vitro functional assays and in vivo xenograft models in female BALB/c nude mice.Results MYBL2 was significantly overexpressed in LSCC tissues and correlated with poor prognosis. Mechanistically, MYBL2 directly activates GTSE1 transcription. This regulation stimulates PI3K/AKT signaling to upregulate key glycolytic proteins (PKM2, HK2, GLUT1, LDHA), thereby driving metabolic reprogramming characterized by elevated glycolysis (ECAR) and suppressed mitochondrial respiration (OCR). Functionally, MYBL2 overexpression enhanced the proliferation, migration, and invasion of LSCC cells in vitro and promoted tumor growth in vivo. Importantly, these oncogenic effects were effectively reversed by GTSE1 knockdown or PI3K inhibition with LY294002, validating the pathway's functional significance.Conclusion The MYBL2-GTSE1 axis promotes LSCC progression through PI3K/AKT-mediated metabolic reprogramming, representing a promising therapeutic target.

Source: Cancer Biology & Therapy

DOI: 10.1080/15384047.2026.2648193