Epithelial-to-mesenchymal transition and its role in EGFR-mutant lung adenocarcinoma and idiopathic pulmonary fibrosis.

Lung adenocarcinoma cells with activating epidermal growth factor receptor (EGFR) mutations are highly dependent upon EGFR signaling for survival and undergo apoptosis when EGFR signaling is inhibited by tyrosine kinase inhibitor (TKI) treatment. Paradoxically, EGFR-mutant lung adenocarcinomas have subpopulations of cells that can survive independently of activated EGFR. Such EGFR-independent EGFR-mutant cancer cells include cells that have undergone epithelial-to-mesenchymal transition (EMT) or transformed to small cell lung cancer, which almost completely lack EGFR dependency. The presence of such cells suggests that EGFR TKIs cannot eradicate EGFR-mutant lung adenocarcinoma cells. However, little is known about whether and to what extent normal peripheral lung epithelial cells, not lung adenocarcinoma cells, can undergo EMT. We have recently reported that normal peripheral lung epithelial cells can undergo dynamic EMT within 72 h in response to transforming growth factor-β signaling. This finding reinforced the hypothesis that alveolar epithelial cells that have undergone EMT contribute to the formation of fibroblastic foci, the leading edge of fibrotic destruction in lungs affected by idiopathic pulmonary fibrosis. This review focuses on the role of EMT in neoplastic and non-neoplastic peripheral lung epithelial cells. .