Role of SIRT5 in cancer. Friend or Foe?

Abstract

Cancer is one of the main diseases currently afflicting mankind, being difficult to treat and generating thousands of deaths per year. As a result, researchers around the world are constantly searching for new therapeutic strategies to increase the survival rate of patients. In this regard, SIRT5 may be a promising therapeutic target due to its involvement in many metabolic pathways. Notably, SIRT5 has a dual role in the context of cancer, being able to act as a tumor suppressor in some types of cancer and behaving as an oncogene in others. Interestingly, the performance of SIRT5 is not specific and is highly dependent on the cellular context. As a tumor suppressor, SIRT5 prevents the Warburg effect, increases protection against ROS and reduces cell proliferation and metastasis, while as an oncogene it has the opposite effects as well as increasing resistance to chemotherapeutics and/or radiation. In this way, the aim of this work was to identify in which cancers SIRT5 has beneficial effects and in which deleterious ones based on their molecular characteristics. Furthermore, it was analyzed whether it is feasible to use this protein as a therapeutic target, either enhancing its activity or inhibiting it as appropriate.