P2X7 receptor promotes non-small cell lung cancer progression through CCL8/CCR5-mediated activation of mTOR and ERK signaling

This study aims to elucidate the role and mechanisms of the P2X7 receptor (P2X7R) in non-small cell lung cancer (NSCLC). By overexpressing or knocking down P2X7R in human A549 and H1703 cells, combined with interventions using BzATP, A438079, and the CCR5 inhibitor Mvc, we systematically evaluated changes in cell proliferation, apoptosis, migration, invasion, and EMT. Results demonstrated that P2X7R activation significantly promoted tumor cell proliferation, migration, and invasion, inhibited apoptosis, and induced EMT, whereas receptor knockdown produced opposite effects. mRNA sequencing and qPCR/ELISA data indicated that P2X7R upregulates CCL8 and its receptor CCR5, further activating ERK and mTOR signaling pathways. Cytoskeletal staining confirmed that P2X7R enhances F-actin remodeling capacity via the CCL8/CCR5 pathway. In tumor-bearing mouse models, P2X7R overexpression promoted tumor growth, whereas knockdown significantly inhibited tumor formation. Collectively, P2X7R drives NSCLC progression by activating the CCL8/CCR5 pathway and its downstream ERK and mTOR signaling, positioning it as a potential therapeutic target.