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

•GRIM-19 interacts with other tumor suppressors to control cell growth.•GRIM-19 inhibits oncoproteins and viral gene products during tumorigenesis.•GRIM-19 regulates glucose utilization and immune responses in pathological settings.

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.

Graphical abstractThe review describes how GRIM-19, a mitochondrial protein, controls tumorigenesis at multiple levels.