title: AMP-activated protein kinase α2 protects against liver injury from metastasized tumors via reduced glucose deprivation-induced oxidative stress.
abstract: It is well known that tumors damage affected tissues; however, the specific mechanism underlying such damage remains elusive. AMP-activated protein kinase (AMPK) senses energetic changes and regulates glucose metabolism. In this study, we examined the mechanisms by which AMPK promotes metabolic adaptation in the tumor-bearing liver using a murine model of colon cancer liver metastasis. Knock-out of AMPK α2 significantly enhanced tumor-induced glucose deprivation in the liver and increased the extent of liver injury and hepatocyte death. Mechanistically, we observed that AMPK α2 deficiency resulted in elevated reactive oxygen species, reduced mitophagy, and increased cell death in response to tumors or glucose deprivation in vitro. These results imply that AMPK α2 is essential for attenuation of liver injury during tumor metastasis via hepatic glucose deprivation and mitophagy-mediated inhibition of reactive oxygen species production. Therefore, AMPK α2 might represent an important therapeutic target for colon cancer metastasis-induced liver injury.
authors: From the Key Laboratory of Remodeling-related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing 100029, China.
authors: Shu-Lan
authors: SL
authors: Qiu
authors: Zhi-Cheng
authors: ZC
authors: Xiao
authors: Chun-Mei
authors: CM
authors: Piao
authors: Ying-Lin
authors: YL
authors: Xian
authors: Li-Xin
authors: LX
authors: Jia
authors: Yong-Fen
authors: YF
authors: Qi
authors: Jia-Huai
authors: JH
authors: Han
authors: You-Yi
authors: YY
authors: Zhang
authors: Jie
authors: J
authors: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D004734:Energy Metabolism; D055786:Gene Knockout Techniques; D005947:Glucose / Q000172:deficiency*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D063306:Mitophagy; D009336:Necrosis / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMP-activated kinase (AMPK); Glucose; Metastasis; Oxidative Stress; Tumor