Haploinsufficiency of SIRT1 Enhances Glutamine Metabolism and Promotes Cancer Development.

ABSTRACT: SIRT1, the most conserved mammalian NAD⁺-dependent protein deacetylase, plays a vital role in the regulation of metabolism, stress responses, and genome stability. However, the role of SIRT1 in the multi-step process leading to transformation and/or tumorigenesis, as either a tumor suppressor or tumor promoter, is complex and may be dependent upon the context in which SIRT1 activity is altered, and the role of SIRT1 in tumor metabolism is unknown. Here, we demonstrate that SIRT1 dose-dependently regulates cellular glutamine metabolism and apoptosis, which in turn differentially impact cell proliferation and cancer development. Heterozygous deletion of Sirt1 induces c-Myc expression, enhancing glutamine metabolism and subsequent proliferation, autophagy, stress resistance, and ca

SUBMITTER: Ren NSX 

PROVIDER: S-EPMC5319916 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature