PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production - Sorbonne Université Access content directly
Journal Articles Scientific Reports Year : 2019

PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production

Jesús Gómez-Escudero
  • Function : Author
Cristina Clemente
  • Function : Author
Rebeca Acín-Pérez
  • Function : Author
Jaime Millán
  • Function : Author
José Enríquez
Katie Bentley
  • Function : Author
Peter Carmeliet
  • Function : Author
Alicia Arroyo

Abstract

Abstract Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs in pathophysiological contexts such as wound healing, cancer, and chronic inflammatory disease. During sprouting angiogenesis, endothelial tip and stalk cells coordinately remodel their cell-cell junctions to allow collective migration and extension of the sprout while maintaining barrier integrity. All these processes require energy, and the predominant ATP generation route in endothelial cells is glycolysis. However, it remains unclear how ATP reaches the plasma membrane and intercellular junctions. In this study, we demonstrate that the glycolytic enzyme pyruvate kinase 2 (PKM2) is required for sprouting angiogenesis in vitro and in vivo through the regulation of endothelial cell-junction dynamics and collective migration. We show that PKM2-silencing decreases ATP required for proper VE-cadherin internalization/traffic at endothelial cell-cell junctions. Our study provides fresh insight into the role of ATP subcellular compartmentalization in endothelial cells during angiogenesis. Since manipulation of EC glycolysis constitutes a potential therapeutic intervention route, particularly in tumors and chronic inflammatory disease, these findings may help to refine the targeting of endothelial glycolytic activity in disease.

Dates and versions

hal-03972086 , version 1 (03-02-2023)

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Jesús Gómez-Escudero, Cristina Clemente, Diego García-Weber, Rebeca Acín-Pérez, Jaime Millán, et al.. PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production. Scientific Reports, 2019, 9 (1), pp.15022. ⟨10.1038/s41598-019-50866-x⟩. ⟨hal-03972086⟩
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