title: SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway.
abstract: Stearoyl-CoA desaturase 1 (SCD1) is a key regulator in the mechanisms of cell proliferation, survival and transformation to cancer, and autophagy also plays a critical role in hepatocellular carcinoma (HCC). However, whether SCD1 mediates autophagy in HCC remains unknown. In this study, we observed significantly elevated SCD1 expression levels and evident suppression of autophagy in HCC, and the positive SCD1 expression and autophagy defect were independently correlated with poor prognosis of HCC patients. We also found that the inhibition of SCD1 by a pharmacological inhibitor reduced cell viability and induced apoptosis and autophagy of human HCC cells in a dose- and time-dependent manner. Moreover, the pharmacological inhibition of AMPK supported the hypothesis that the induction of autophagy caused by SCD1 inhibition relied on AMPK stimulation. Furthermore, the human HCC cells death triggered by inhibition of SCD1 was partly involved in autophagy-induced apoptosis via AMPK signaling. Our findings reveal a novel role for SCD1 in the regulation of autophagy via AMPK signaling and provide mechanistic input for the clinical exploration that the combination of SCD1 inhibition with autophagy induction may be attractive for the management of HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Dazhou Hospital of Integrated Traditional and Western Medicine, Dazhou, Sichuan 635000, China.
authors.forename: Qing-Hu
authors.initials: QH
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Can
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Qu
authors.affiliation: Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: shenwei315@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Autophagy; Hepatocellular carcinoma; SCD1