Boyineni Jerusha, Sredni Simone T, Margaryan Naira V, Demirkhanyan Lusine, Tye Michael, Johnson Robert, Gonzalez-Nilo Fernando, Hendrix Mary J C, Pavlov Evgeny, Soares Marcelo B, Zakharian Eleonora, Malchenko Sergey
Department of Cancer Biology & Pharmacology, University of Illinois College of Medicine, Peoria, Illinois, USA.
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Oncotarget. 2020 Dec 15;11(50):4613-4624. doi: 10.18632/oncotarget.27838.
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.
癌细胞对能量有很高的需求以维持其极度增殖性生长。然而，癌症中能量消耗的机制尚未完全了解。我们推测癌细胞可能利用富含能量的无机多聚磷酸盐（多聚磷酸）作为能量储备。多聚磷酸由通过磷酸酐键连接的正磷酸盐组成，就像ATP一样。在这里，我们表明多聚磷酸在几种类型的癌细胞中高度丰富，包括脑肿瘤起始细胞（BTICs），即源自我们之前描述的小鼠脑肿瘤模型的干细胞样细胞。在BTICs饥饿期间，这种聚合物被大量消耗。通过抑制糖酵解和线粒体ATP合酶（氧化磷酸化）来耗尽ATP会进一步降低多聚磷酸的水平并改变细胞形态。此外，该聚合物的酶促水解会损害癌细胞的活力并显著耗尽ATP储备。这些结果表明多聚磷酸可能在癌症中被用作磷酸盐能量的来源。虽然多聚磷酸作为能量来源在细菌中的作用已得到证实，但这一发现首次证明多聚磷酸可能在癌细胞代谢中发挥类似作用。
