Work

KO of 5-InsP 7 kinase activity transforms the HCT116 colon cancer cell line into a hypermetabolic, growth-inhibited phenotype

Year: 2017

Type: article

Abstract: Significance Therapeutic improvements to human health can accrue from understanding the bidirectional relationship between cell signaling and bioenergetic homeostasis. Key players in this communication interface are inositol pyrophosphate cellular signals 5-InsP 7 and 1,5-InsP 8 , which are interconverted by diphosphoinositol pentakisphosphate kinases (PPIP5Ks). Here, an intestinal tumor cell line is used for CRISPR-based KO of PPIP5Ks, which eliminates 1,5-InsP 8 and raises 5-InsP 7 levels several fold. PPIP5K −/− cells exhibit a growth-inhibited phenotype, indicating that PPIP5Ks are potential targets for tumor therapy. PPIP5K −/− cells also have elevated levels of ATP because of increased mitochondrial biomass and accelerated rates of glycolysis. This hypermetabolic state is attributed to hitherto unsuspected functions for 1,5-InsP 8 in bioenergetic homeostasis, thereby suggesting that PPIP5Ks could offer approaches to treat metabolic diseases.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1702370114