Oncotarget: Inorganic polyphosphate as an energy source in tumorigenesis

Oncotarget published "Inorganic polyphosphate as an energy source in tumorigenesis" which reported that Cancer cells have high demands for energy to maintain their exceedingly proliferative growth.

Here, the authors show that polyP is highly abundant in several types of cancer cells, including brain tumor-initiating cells , i.e., stem-like cells derived from a mouse brain tumor model that we have previously described.

Moreover, enzymatic hydrolysis of the polymer impairs the viability of cancer cells and significantly deprives ATP stores.

These Oncotarget results suggest that polyP might be utilized as a source of phosphate energy in cancer.

These Oncotarget 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.

Dr. Eleonora Zakharian and Dr. Sergey Malchenko from The University of Illinois College of Medicine said, "Evolutionarily, the eukaryotic genome resulted from endosymbiosis between the progenitor of the eukaryotic lineage and an aerobic proteobacterium–the origin of mitochondria"

The unique advantage of polyP as an energy source is that it can be directly converted into ATP without any intermediate steps and it does not require oxygen to generate energy.

Among numerous functions of polyP, one of the most evolutionary fascinating is its contribution to energy metabolism.

Figure 5: (A and B) Morphology and cellular size of LC26-10R (RG) and LC26- RTL(4) (BTICs) after 3 h and 6 h starvation, IAA, or IAA/Oligomycin treatment. PolyP staining (green). RedDot2 (red) nuclear staining.

In higher eukaryotes, polyP is involved in regulation of different mitochondrial functions, including regulation of intracellular ATP.

It was shown recently that incubation of synthetic polyP with human osteogenic sarcoma cells led to accumulation of ADP and ATP in the extracellular space of the cells.

In particular, this study shows that polyP could be utilized in these cells as a source of phosphate energy.

The Zakharian/Malchenko Research Team concluded in their Oncotarget Research Output, "In contrast to bacteria, the triggering mechanisms and the corresponding eukaryotic pathways responsible for the synthesis and degradation of polyP have been largely unknown [21, 41, 42]. We anticipate that future studies will reveal the direct link between polyP accumulation, cellular bioenergetics and tumorigenesis. If so, a new field of human polyP metabolism regulation will emerge, providing the opportunity to exploit polyP as a targetable cancer-specific energy source."

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DOI - https://doi.org/10.18632/oncotarget.27838

Full text - https://www.oncotarget.com/article/27838/text/

Correspondence to - Eleonora Zakharian - zakharel@uic.edu and Sergey Malchenko - sergeynm@uic.edu

Keywords - polyphosphate, energy source, OXPHOS, glycolysis, metabolism

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