Molecular Mechanisms of E-Cadherin in Lung Cancer: A Literature Review

Lung cancer remains the most common cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases. Despite advances in molecularly targeted therapy and immunotherapy, survival rates remain poor, particularly in advanced stages. E-cadherin, a calcium-dependent adhesion molecule, plays a central role in maintaining epithelial tissue integrity. Its loss or dysfunction is strongly associated with tumor progression, invasion, and poor prognosis. This review aims to systematically analyze the molecular mechanisms of E-cadherin dysregulation in lung cancer, its prognostic significance, and its interactions with key signaling pathways. Relevant articles were identified through PubMed, Scopus, and Web of Science, using the keywords “E-cadherin,” “non-small cell lung cancer,” “prognosis,” and “molecular mechanism.” Studies published between 2000 and 2023 were included. Data were synthesized narratively with emphasis on immunohistochemical evidence, signaling crosstalk, and clinical outcomes. Downregulation of E-cadherin was consistently correlated with poor tumor differentiation, higher metastatic potential, and reduced survival in NSCLC patients. Mechanistically, loss of E-cadherin induces epithelial–mesenchymal transition (EMT) through Wnt/β-catenin, Snail, Slug, and TGF-β pathways. Crosstalk with EGFR signaling destabilizes E-cadherin, enhancing tumor proliferation and invasion. E-cadherin plays a dual role in NSCLC: as a structural adhesion molecule maintaining epithelial integrity and as a regulator of signaling networks driving tumor progression and immune evasion. Its downregulation is both a marker and a driver of poor outcomes.