Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity - Aix-Marseille Université Access content directly
Journal Articles Life Science Alliance Year : 2018

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

Konrad J. Mostert
  • Function : Author
Thomas Gensollen
  • Function : Author
Binta Dieme
Noudjoud Attaf-Bouabdallah
  • Function : Author
Erick Strauss
  • Function : Author
Philippe Naquet

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.
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hal-02077009 , version 1 (26-05-2020)

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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, 2018, 1 (4), ⟨10.26508/lsa.201800073⟩. ⟨hal-02077009⟩
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