Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway.

This article focuses on the molecular mechanisms by which high-risk human papillomavirus (HPV), particularly the E6 oncoprotein, contributes to cervical cancer (CC) progression through dysregulation of glucose-6-phosphate dehydrogenase (G6PD) and activation of the STAT3/PLOD2 pathway. Proteomic analyses of cervical tissues and cell lines revealed elevated levels of HPV E6, G6PD, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (pSTAT3), and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in HPV-positive CC samples. Functional experiments demonstrated that HPV E6-induced upregulation of G6PD enhances CC cell proliferation, migration, and invasion while inhibiting apoptosis, primarily via STAT3-mediated activation of PLOD2. These findings elucidate a novel HPV E6-G6PD-STAT3-PLOD2 axis in cervical carcinogenesis and suggest potential therapeutic targets within this pathway.