CDH3 promotes the progression of lung adenocarcinoma through driving epithelial-mesenchymal transition progress

Cadherin-3 (CDH3) participates in multiple oncogenic processes, but its biological role and mechanisms in lung adenocarcinoma (LUAD) remain inadequately understood. We analyzed CDH3 expression in LUAD versus adjacent normal tissues and assessed its association with patient outcomes. Bioinformatics, immune scoring, and single-cell analysis were used to explore CDH3's links to epithelial-mesenchymal transition (EMT), inflammatory responses, TNF pathway activation, glycolysis, hypoxia, and tumor-associated macrophage infiltration. Independent immunotherapy datasets (IMvigor210, GSE91061) were evaluated for CDH3's relationship to treatment response. In vitro CDH3 knockdown studies assessed effects on glycolysis, EMT, proliferation, and migration in LUAD cells, and in vivo tumor growth was measured post-knockdown. CDH3 expression was significantly elevated in LUAD tissues and correlated with poorer patient survival. High CDH3 expression associated with EMT, inflammatory responses (including TNF pathway), glycolysis, and hypoxia. It also promoted tumor-associated macrophage infiltration and impaired anti-tumor immunity. Patients with low CDH3 expression showed improved immunotherapy response and prognosis. CDH3 knockdown suppressed LUAD cells glycolysis process, EMT, proliferation, and migration in vitro, and significantly repressed tumor growth in vivo. CDH3 drives LUAD progression by promoting EMT, tumor growth, metastasis, and immunosuppression. It represents a promising diagnostic/prognostic biomarker and a novel therapeutic target for LUAD immunotherapy.