PDLIM7 promotes the progression of lung adenocarcinoma by activating the mTORC1 pathway and glycolysis.

BACKGROUND: The PDZ and LIM domain 7 (PDLIM7) has been reported to play a critical role in cancer progression, but its specific role and underlying mechanisms in lung adenocarcinoma (LUAD) remain unexplored. METHODS: We investigated PDLIM7 in LUAD using bioinformatics tools, cell counting kit-8, colony formation, flow cytometry, wound healing assay, transwell, western blotting, glucose uptake, lactate production assay, and seahorse extracellular flux analysis. Rescue experiments with mTOR inhibitor rapamycin and constitutively active S6K1 (caS6K1) were performed to verify the mechanism by which PDLIM7 drives LUAD progression. In addition, in vivo mouse models were conducted to explore the effects of PDLIM7 on tumor growth. RESULTS: PDLIM7 expression was elevated in LUAD tissues and correlated with a poor overall survival. PDLIM7 knockdown inhibited LUAD cell proliferation, migration, invasion, and glycolysis, but promoted cell apoptosis. However, its overexpression produced the opposite effects. Mechanistically, PDLIM7 drove LUAD progression via mTORC1 activation, as evidenced by the findings that rapamycin abrogated the promoting effects of PDLIM7 overexpression on proliferation, invasion, and glycolysis, while caS6K1 counteracted the inhibition of proliferation, invasion, and glycolysis resulting from PDLIM7 knockdown. Furthermore, in a xenograft mouse model, PDLIM7 knockdown suppressed tumor growth, while PDLIM7 overexpression promoted tumor growth. The enhanced tumor growth induced by PDLIM7 overexpression was abrogated by treatment with the mTORC1 inhibitor rapamycin. CONCLUSIONS: PDLIM7 promotes LUAD progression by activating the mTORC1 signaling pathway and glycolysis.