p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas.

摘要: Squamous cell carcinoma (SCC), a malignancy arising across multiple anatomical sites, is responsible for significant cancer mortality due to insufficient therapeutic options. Here, we identify exceptional glucose reliance among SCCs dictated by hyperactive GLUT1-mediated influx. Mechanistically, squamous lineage transcription factors p63 and SOX2 transactivate the intronic enhancer cluster of SLC2A1. Elevated influx fuels generation NADPH GSH, thereby heightening anti-oxidative capacity in SCC tumors. Systemic restriction ketogenic diet inhibiting renal reabsorption with SGLT2 inhibitor precipitate intratumoral oxidative stress tumor growth inhibition. Furthermore, reduction blood lowers insulin levels, which suppresses PI3K/AKT signaling cells. Clinically, demonstrate robust correlation between concentration worse survival patients. Collectively, this study identifies suggests its candidacy as highly vulnerable type be targeted systemic restriction.