RT Journal Article SR Electronic T1 Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800073 DO 10.26508/lsa.201800073 VO 1 IS 4 A1 Caroline Giessner A1 Virginie Millet A1 Konrad J Mostert A1 Thomas Gensollen A1 Thien-Phong Vu Manh A1 Marc Garibal A1 Binta Dieme A1 Noudjoud Attaf-Bouabdallah A1 Lionel Chasson A1 Nicolas Brouilly A1 Caroline Laprie A1 Tom Lesluyes A1 Jean Yves Blay A1 Laetitia Shintu A1 Jean Charles Martin A1 Erick Strauss A1 Franck Galland A1 Philippe Naquet YR 2018 UL https://www.life-science-alliance.org/content/1/4/e201800073.abstract AB Like other tumors, aggressive soft tissue sarcomas (STS) use glycolysis rather than mitochondrial oxidative phosphorylation (OXPHOS) for growth. Given the importance of the cofactor coenzyme A (CoA) in energy metabolism, we investigated the impact of Vnn1 pantetheinase—an enzyme that degrades pantetheine into pantothenate (vitamin B5, the CoA biosynthetic precursor) and cysyteamine—on tumor growth. Using two models, we show that Vnn1+ STS remain differentiated and grow slowly, and that in patients a detectable level of VNN1 expression in STS is associated with an improved prognosis. Increasing pantetheinase activity in aggressive tumors limits their growth. Using combined approaches, we demonstrate that Vnn1 permits restoration of CoA pools, thereby maintaining OXPHOS. The simultaneous production of cysteamine limits glycolysis and release of lactate, resulting in a partial inhibition of STS growth in vitro and in vivo. We propose that the Warburg effect observed in aggressive STS is reversed by induction of Vnn1 pantetheinase and the rewiring of cellular energy metabolism by its products.