ACADL suppresses PD-L1 expression to prevent cancer immune evasion by targeting Hippo/YAP signaling in lung adenocarcinoma.

Li Li, Ling-Ling Wang, Tao-Li Wang, Fei-Meng Zheng

Medical oncology (Northwood, London, England) 2023 Mar 17

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Lung cancer is the leading cause of cancer-related death. Cancer immune evasion is a key barrier in the treatment of lung cancer and the development of effective anticancer therapeutics. Long-chain Acyl-CoA dehydrogenase (ACADL), a key enzyme that regulates β-oxidation of long-chain fatty acyl-CoAs, has been found to act as a tumor suppressor in cancers. However, the role of ACADL in lung adenocarcinoma (LUAD) has not been explored. In the current study, we find that ACADL functions as a tumor suppressor in LUAD to inhibit proliferation and enhanced chemotherapeutic drug-induced apoptosis. Interestingly, ACADL prevents tumor immune evasion by suppressing PD-L1 expression in LUAD. ACADL is critical for Hippo/YAP pathway-mediated PD-L1 regulation. Moreover, YAP activation is essential for ACADL suppression of PD-L1 transcription. In addition, ACADL increases the protein stability and kinase activity of LATS kinase to inhibit YAP activation and PD-L1 transcription. Furthermore, we show that ACADL expression is positively correlated with a better OS and FP in LUAD. Our data reveals that ACADL could be a promising target for regulating Hippo/YAP pathway to prevent tumor immune evasion in LUAD. © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Li Li, Ling-Ling Wang, Tao-Li Wang, Fei-Meng Zheng. ACADL suppresses PD-L1 expression to prevent cancer immune evasion by targeting Hippo/YAP signaling in lung adenocarcinoma. Medical oncology (Northwood, London, England). 2023 Mar 17;40(4):118