LAMB3 orchestrates EGFR-MAPK-PKM cascade to promote glycolytic reprogramming and progression in laryngeal carcinoma.

Laryngeal carcinoma (LC) remains a challenging malignancy with poor prognosis, necessitating the identification of novel therapeutic targets. This study investigates the functional role and underlying mechanism of the extracellular matrix protein Laminin Subunit Beta-3 (LAMB3) in LC progression. Bioinformatics analysis of multiple GEO datasets demonstrated that LAMB3 is significantly overexpressed in LC tissues and that high LAMB3 expression correlates with reduced overall survival in patients. Functional validation using two distinct LC cell lines revealed that knockdown of LAMB3 potently suppresses cellular proliferation, migration, clonogenic capacity, and glycolytic metabolism in vitro, and inhibits tumor growth in xenograft models. Mechanistically, we identified that LAMB3 activates the EGFR-MAPK signaling axis, increasing the phosphorylation of EGFR and ERK, leading to transcriptional upregulation of the key glycolytic enzyme PKM, resulting in enhanced glycolytic flux, as evidenced by increased glucose uptake and lactate production. Critically, the oncogenic effects of LAMB3 are entirely dependent on this axis; both genetic silencing of PKM and pharmacological inhibition of the EGFR or MAPK abrogate LAMB3-driven glycolytic reprogramming and tumor-promoting phenotypes in vitro and in vivo. Our findings establish LAMB3 as a novel prognostic biomarker and reveal the LAMB3-EGFR-MAPK-PKM signaling axis as a promising therapeutic target for intervention in laryngeal carcinoma.