Cells under stressed conditions of hypoxia and glucose depletion turn to other biomolecules to fulfill their energy needs. One such biomolecule is acetate which can be sourced directly from the circulation or freed up within cells by the action of stress activated enzymes. Acetate is readily converted to acetyl CoA that enables numerous cellular functions.
Survival requires dynamic reprogramming and rebuilding of cellular machinery to deal with the challenges of the new environment. This is achieved by epigenetic gene expression programs that are activated by acetylating master genes in the nucleus that redirect cellular priorities to overcome the environmental stress.
Studies demonstrating that tumor cells take up significant amounts of acetate often in preference to glucose has led to the investigation of acetate metabolism in cancer and stress. The inner tumor mass is a poorly vascularized nutritionally barren region in which cells survive by rewiring their metabolism. The propensity of certain tumors to take up acetate has been exploited by using 11C-acetate guided positron emission tomography (PET) imaging for the detection of primary tumors and distant metastases. In fact, 11C-acetate guided PET has been reported to be more efficient than labeled 18Fluoro-Deoxy Glucose (18FDG) in detecting or grading gliomas, hepatocellular carcinomas, non-small cell lung cancer and metastases in prostate cancer patients.