CSN5 overexpression promotes the integral progression of cervical cancer by enhancing ENO3-mediated glycolysis.

Cervical cancer (CC) remains a significant global health challenge. A deeper understanding of the molecular mechanisms driving CC progression is crucial for developing improved therapeutic strategies. CSN5 is vital in cell functions and cancer, but its role in CC is unclear. This study aims to explore CSN5's role and its target gene in CC progression, assessing their potential as therapeutic targets. We employed an integrated approach combining bioinformatics analysis, proteomic profiling, and in vitro and in vivo functional assays. Immunohistochemistry was used to analyze CSN5 and ENO3 expression in CC and normal tissues. CSN5 upregulation was associated with advanced clinical stage and poor differentiation. Furthermore, CSN5 overexpression enhanced cellular proliferation and glycolytic metabolism but, paradoxically, suppressed migration, invasion, and the epithelial-mesenchymal transition (EMT). These pro-tumorigenic effects were confirmed in vivo, and the glycolytic inhibitor 2-DG was found to reverse the phenotypes induced by CSN5. Protein sequencing highlighted ENO3's role in CSN5-mediated tumorigenesis, regulating EMT and glycolysis by stabilizing its ubiquitination degradation through CSN5. Crucially, silencing ENO3 attenuated the oncogenic effects of CSN5 both in vitro and in vivo. Our findings unveil a novel mechanistic paradigm in which CSN5 promotes CC progression by co-opting ENO3 to enhance glycolytic flux while concurrently suppressing cell motility. This study not only deepens the understanding of CC pathogenesis but also identifies the CSN5-ENO3 axis as a promising target for novel therapeutic interventions.