2013
DOI: 10.1016/j.bbadis.2013.04.003
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V-ATPase is a candidate therapeutic target for Ewing sarcoma

Abstract: Suppression of oxidative phosphorylation combined with enhanced aerobic glycolysis and the resulting increased generation of protons are common features of several types of cancer. An efficient mechanism to escape cell death resulting from intracellular acidification is proton pump activation. In Ewing sarcoma (ES), although the tumor-associated chimeric gene EWS-FLI1 is known to induce the accumulation of hypoxia-induced transcription factor HIF-1α, derangements in metabolic pathways have been neglected so fa… Show more

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Cited by 60 publications
(53 citation statements)
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References 58 publications
(76 reference statements)
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“…In BM-MSC, we did not find any significant difference in the expression of senescence related genes, while the expression of genes related to stress response was significantly increased, confirming our previous results (Avnet et al, 2017). Moreover, as we have already demonstrated in cancer cells of mesenchymal origin (Avnet et al, 2013;, acidic pHe did not increase cell apoptosis in normal cells of the same origin: short-term exposure to acidic pHe induced the expression of anti-apoptotic genes and the expression of pro-apoptotic genes was not affected. In addition, the number of apoptotic cells with pyknotic nuclei in DPSC and BM-MSC cultures was significantly reduced at pH 6.5 vs. pH 7.4.…”
Section: Discussionmentioning
confidence: 56%
“…In BM-MSC, we did not find any significant difference in the expression of senescence related genes, while the expression of genes related to stress response was significantly increased, confirming our previous results (Avnet et al, 2017). Moreover, as we have already demonstrated in cancer cells of mesenchymal origin (Avnet et al, 2013;, acidic pHe did not increase cell apoptosis in normal cells of the same origin: short-term exposure to acidic pHe induced the expression of anti-apoptotic genes and the expression of pro-apoptotic genes was not affected. In addition, the number of apoptotic cells with pyknotic nuclei in DPSC and BM-MSC cultures was significantly reduced at pH 6.5 vs. pH 7.4.…”
Section: Discussionmentioning
confidence: 56%
“…In this context, acidic tumor microenvironment promotes in tumor cells a low-proliferating phenotype, which does not revert even in the presence of a high level of growth factors [23]. It has also been shown by several reports that extracellular acidosis increases the percentage of cells in G0 phase [24]. Indeed, exposure to acidosis alters growth factor signaling and reduces serum ability to stimulate Raf/ERK/mTORC1 kinase pathway [25].…”
Section: How Low Ph May Contribute To Dormancy Of Tumor Cells Aciditymentioning
confidence: 95%
“…Increased cancer cell invasive activity is frequently associated with aberrant V‐ATPase plasma membrane localization suggesting that increased acidification of the extracellular space plays an important role 29, 33, 34, 37, 47, 48, 49, 50, 51, 52…”
Section: V‐atpase Function In Cancer Cellsmentioning
confidence: 99%