Inorganic polyphosphate as an energy source in tumorigenesis

Jerusha Boyineni, Simone T. Sredni, Naira V. Margaryan, Lusine Demirkhanyan, Michael Tye, Robert Johnson, Fernando Gonzalez-Nilo, Mary J.C. Hendrix, Evgeny Pavlov, Marcelo B. Soares, Eleonora Zakharian, Sergey Malchenko

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

Cancer cells have high demands for energy to maintain their exceedingly proliferative growth. However, the mechanism of energy expenditure in cancer is not well understood. We hypothesize that cancer cells might utilize energy-rich inorganic polyphosphate (polyP), as energetic reserve. PolyP is comprised of orthophosphates linked by phosphoanhydride bonds, as in ATP. Here, we show that polyP is highly abundant in several types of cancer cells, including brain tumor-initiating cells (BTICs), i.e., stem-like cells derived from a mouse brain tumor model that we have previously described. The polymer is avidly consumed during starvation of the BTICs. Depletion of ATP by inhibiting glycolysis and mitochondrial ATP-synthase (OXPHOS) further decreases the levels of polyP and alters morphology of the cells. Moreover, enzymatic hydrolysis of the polymer impairs the viability of cancer cells and significantly deprives ATP stores. These results suggest that polyP might be utilized as a source of phosphate energy in cancer. While the role of polyP as an energy source is established for bacteria, this finding is the first demonstration that polyP may play a similar role in the metabolism of cancer cells.

Idioma originalInglés
Páginas (desde-hasta)4613-4624
Número de páginas12
PublicaciónOncotarget
Volumen11
N.º50
DOI
EstadoPublicada - 15 dic 2020

Áreas temáticas de ASJC Scopus

  • Oncología

Huella

Profundice en los temas de investigación de 'Inorganic polyphosphate as an energy source in tumorigenesis'. En conjunto forman una huella única.

Citar esto