Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity

Abstract : 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.
Document type :
Journal articles
Complete list of metadata

Cited literature [69 references]  Display  Hide  Download
Contributor : Annick Prémilleux Connect in order to contact the contributor
Submitted on : Tuesday, May 26, 2020 - 5:38:23 PM
Last modification on : Friday, February 18, 2022 - 3:38:11 PM


Publisher files allowed on an open archive


Distributed under a Creative Commons Attribution 4.0 International License



Caroline Giessner, Virginie Millet, Konrad J. Mostert, Thomas Gensollen, Thien-Phong Vu Manh, et al.. Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity. Life Science Alliance, Life Science Alliance LLC, 2018, 1 (4), ⟨10.26508/lsa.201800073⟩. ⟨hal-02077009⟩



Record views


Files downloads