MOL Highlight: Cross-Talk between Alternatively Spliced UGT1A Isoforms and Colon Cancer Cell Metabolism
Audet-Delage et al. demonstrate that an alternatively spliced form of human glucuronosyltransferase 1, known to control glucuronidation activity via protein-protein interactions, also functionally interacts with key enzymes in metabolic pathways co-opted by cancer. One such target is the rate-limiting enzyme of glycolysis, pyruvate kinase. Depletion of the splice variant enforces the Warburg effect (a high glycolytic rate at the expense of mitochondrial respiration needed to fuel the activities of cancer cells) and leads to lactate accumulation. Many metabolites derived from the glycolytic and tricarboxylic acid cycle pathways were affected in a manner consistent with greater metastatic potential by the selective down-regulation of the splice variant in colon tumors. Glucuronosyltransferase 1 splice variants may thus be part of an expanding number of metabolic pathways known to be involved in contributing to the oncogenic phenotype of colon cancer cells.
See the article by Audet-Delage et al. at Molecular Pharmacology March 2017, 91 (3) 167-177; DOI: https://doi.org/10.1124/mol.116.106161