CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation.

ABSTRACT: Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-def

SUBMITTER: Miller TW 

PROVIDER: S-EPMC4598996 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature