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ACADL plays a tumor-suppressor role by targeting Hippo/YAP signaling in hepatocellular carcinoma.


ABSTRACT: Long-chain acyl-CoA dehydrogenase (ACADL) is a mitochondrial enzyme that catalyzes the initial step of fatty acid oxidation, but the role of ACADL in tumor biology remains largely unknown. Here, we found that ACADL was frequently downregulated in hepatocellular carcinoma (HCC), and its low expression was significantly correlated with poor clinical prognosis of HCC patients. Restoring the expression of ACADL in HCC cells resulted cell cycle arrest and growth suppression through suppressing Hippo/YAP signaling evidenced by decreased YAP nuclear accumulation and downstream target genes expression. Reactivation of YAP by XMU-MP-1 diminished the inhibitory effect of ACADL on HCC growth. More importantly, the nuclear accumulation of YAP was negatively correlated with ACADL expression levels in HCC specimens, and YAP inhibitor verteporfin effectively suppressed growth of HCC organoids with low ACADL expression. Together, our findings highlight a novel function of ACADL in regulating HCC growth and targeting ACADL/Yap may be a potential strategy for HCC precise treatment.

SUBMITTER: Zhao X 

PROVIDER: S-EPMC7096519 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ACADL plays a tumor-suppressor role by targeting Hippo/YAP signaling in hepatocellular carcinoma.

Zhao Xiaofang X   Qin Wenhao W   Jiang Youhai Y   Yang Zhishi Z   Yuan Bo B   Dai Rongyang R   Shen Hao H   Chen Yao Y   Fu Jing J   Wang Hongyang H  

NPJ precision oncology 20200325


Long-chain acyl-CoA dehydrogenase (ACADL) is a mitochondrial enzyme that catalyzes the initial step of fatty acid oxidation, but the role of ACADL in tumor biology remains largely unknown. Here, we found that ACADL was frequently downregulated in hepatocellular carcinoma (HCC), and its low expression was significantly correlated with poor clinical prognosis of HCC patients. Restoring the expression of ACADL in HCC cells resulted cell cycle arrest and growth suppression through suppressing Hippo/  ...[more]

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