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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4613-4624
Number of pages12
JournalOncotarget
Volume11
Issue number50
DOIs
StatePublished - Dec 15 2020

Keywords

  • Energy source
  • Glycolysis
  • Metabolism
  • OXPHOS
  • Polyphosphate

ASJC Scopus subject areas

  • Oncology

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