PLEK2 mediates metastasis and invasion via α5-nAChR activation in nicotine-induced lung adenocarcinoma.

Abstract

Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5-nicotinic acetylcholine receptor (α5-nAChR) contributes to nicotine-induced lung cancer cell EMT. The cytoskeleton-associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5-nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5-nAChR and PLEK2 in LUAD. α5-nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5-nAChR mediated nicotine-induced PLEK2 expression via STAT3. α5-nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine-induced EMT in LUAD cells. Furthermore, the functional link among α5-nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5-nAChR/PLEK2/CFL1 pathway involved in nicotine-induced LUAD progression.