Metallothionein 2A enhances the yes-associated protein 1 signaling pathway to promote small-cell lung cancer metastasis.

OBJECTIVE: Small-cell lung cancer (SCLC) remains challenging to treat due to its high invasiveness and propensity for drug resistance. Evidence suggests that the regulatory relationship between metallothionein 2A (MT2A) and the yes-associated protein 1 (YAP1) signaling pathway may influence the development of SCLC. Therefore, this study aims to explore the potential mechanisms affecting SCLC progression based on the regulatory interaction between YAP1 and MT2A. MATERIAL AND METHODS: This study utilized reverse transcription quantitative polymerase chain reaction and Western blot analysis to analyze MT2A expression in cells. SCLC cell models with MT2A silencing and overexpression, as well as cotransfected cell models with YAP1 silencing and MT2A overexpression, were constructed. The effect of MT2A/YAP1 on cell growth, migration, and invasion was evaluated through a series of experiments, including cell viability assessment using cell counting kit-8 assay, colony formation examination, 5-ethynyl-2'-deoxyuridine staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Transwell analysis. In addition, Western blot analysis was conducted to investigate alterations in crucial proteins associated with the YAP1 pathway and the epithelial-mesenchymal transition ( EMT) markers influenced by MT2A/YAP1. Lung metastasis and Ki67 expression were analyzed through hematoxylin and eosin staining and immunofluorescence analysis in vivo. RESULTS: In the SCLC cell line ( NCI-H69 cells), MT2A exhibits increased expression, facilitating cell growth, migration, and invasion. YAP1 expression decreases when MT2A is depleted. In addition, our findings validate that MT2A facilitates EMT progression and SCLC invasion and metastasis by upregulating YAP1 expression. In vitro, silencing MT2A inhibits lung metastasis and Ki67 expression. CONCLUSION: MT2A facilitates the migration and invasion of SCLC cells by influencing the YAP1 signaling cascade. This investigation offers a fresh avenue for delving deeply into the potential mechanisms involved in the progression of SCLC.