Carcinoembryonic antigen potentiates non-small cell lung cancer progression via PKA-PGC1ɑ axis

Abstract

Abstract Background Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. CEA has been reported to be involved in various biological processes, including cell adhesion, proliferation, differentiation, and metastasis. However, the impact of CEA on the tumor immune escape remains largely unknown. Methods The A549 tumor-bearing mouse models were established to investigate the role of CEA during tumor progression. CCK-8 assay, Colony formation assay, ELISA, immunohistochemistry and flow cytometry analysis were used to assess the role of CEA on fatty acid metabolism and proliferation of A549 and H1299 cells. Results In this study, we demonstrate that CEA promotes the proliferation and migration of non-small cell lung cancer (NSCLC). Our findings indicate that CEA enhances NSCLC proliferation and migration through the activation of fatty acid metabolism-related genes and PGC1 expression. Mechanistically, CEA promotes PGC1 expression via the PKA-PGC1ɑ signaling pathway. Inhibition of the PKA-PGC1ɑ signaling pathway attenuates CEA-induced proliferation and migration of NSCLC. Interestingly, we also observed that inhibition of PGC1α downregulates the expression of PD-L1 in NSCLC. Conclusion These results reveal the involvement of CEA in fatty acid metabolism during lung cancer development and highlight its impact on immunotherapy of NSCLC.