Anirban Kundu, Garrett J Brinkley, Hyeyoung Nam, Suman Karki, Richard Kirkman, Madhuparna Pandit, EunHee Shim, Hayley Widden, Juan Liu, Yasaman Heidarian, Nader H Mahmoudzadeh, Alexander J Fitt, Devin Absher, Han-Fei Ding, David K Crossman, William J Placzek, Jason W Locasale, Dinesh Rakheja, Jonathan E McConathy, Rekha Ramachandran, Sejong Bae, Jason M Tennessen, Sunil Sudarshan
Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule L-2-hdroxyglutarate (L-2HG) is elevated in the most common histology of renal cancer. Similar to other oncometabolites, L-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that L-2HG remodels amino acid metabolism in renal cancer cells through the combined effects on histone methylation and RNA N6-methyladenosine (m6A)...
May 14, 2024: Journal of Clinical Investigation