AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation-associated AMPKα1 activation

Shulan Qiu, Taoyan Liu, Chunmei Piao, Ying Wang, Kefang Wang, Yandong Zhou, Lun Cai, Shuai Zheng, Feng Lan, Jie Du

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Tissue damage and its associated-inflammation act as tumour initiators or propagators. AMP-activated protein kinase (AMPK) is activated by environmental or nutritional stress factors, such as hypoxia, glucose deprivation, and other cell injury factors, to regulate cell energy balance and differentiation. We previously have reported that AMPKα2 deficiency resulted in the energy deprivation in tumour-bearing liver and the enhanced-hepatocyte death. In this study, AMPKα2 knockout mice and the liver metastasis model of colon cancer cells were used to address the role of AMPKα isoforms in tumour inflammation. First, we found that the AMPKα2 deficiency exacerbated the liver injury and recruitment of macrophages. Meanwhile, although compensatory expression of AMPKα1 was not significant after AMPKα2 knockout, AMPKα1 phosphorylation was elevated in remnant liver in AMPKα2 knockout mice, which was positively associated with the enhanced energy deprivation in the AMPKα2 deficient mice. Furthermore, the activated AMPKα1 in macrophage contributed to its polarizing to tumour-associated phenotype. Thus, the enhanced tumour-associated inflammation and activation of AMPKα1 in the AMPKα2 deficient mice may exacerbate the tumour development by affecting the tumour inflammatory microenvironment. Our study suggests that the two isoforms of AMPKα, AMPKα1 and AMPKα2 play different roles in controlling tumour development.

Original languageEnglish (US)
Pages (from-to)1687-1697
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • AMPKα1
  • AMPKα2 deficiency
  • energy deprivation
  • liver metastasis
  • macrophages

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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