GRIM-19: A master regulator of cytokine induced tumor suppression, metastasis and energy metabolism

Cytokine Growth Factor Rev. 2017 Feb:33:1-18. doi: 10.1016/j.cytogfr.2016.09.001. Epub 2016 Sep 15.

Abstract

Cytokines induce cell proliferation or growth suppression depending on the context. It is increasingly becoming clear that success of standard radiotherapy and/or chemotherapeutics to eradicate solid tumors is dependent on IFN signaling. In this review we discuss the molecular mechanisms of tumor growth suppression by a gene product isolated in our laboratory using a genome-wide expression knock-down strategy. Gene associated with retinoid-IFN-induced mortality -19 (GRIM-19) functions as non-canonical tumor suppressor by antagonizing oncoproteins. As a component of mitochondrial respiratory chain, GRIM-19 influences the degree of "Warburg effect" in cancer cells as many advanced and/or aggressive tumors show severely down-regulated GRIM-19 levels. In addition, GRIM-19 appears to regulate innate and acquired immune responses in mouse models. Thus, GRIM-19 is positioned at nodes that favor cell protection and/or prevent aberrant cell growth.

Keywords: Anti-tumor action; Cell motility; Cytokines; Glucose metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / physiology*
  • Down-Regulation
  • Energy Metabolism
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Glucose / metabolism
  • Mice
  • Mitochondria / metabolism
  • NADH, NADPH Oxidoreductases / genetics*
  • NADH, NADPH Oxidoreductases / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • Cytokines
  • STAT3 Transcription Factor
  • NADH, NADPH Oxidoreductases
  • NDUFA13 protein, human
  • Glucose