کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8260841 | 1534669 | 2013 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
V-ATPase is a candidate therapeutic target for Ewing sarcoma
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کلمات کلیدی
OMEHsp60V-ATPasePHEBECPHIHIFs - HIF هاExtracellular pH - pH خارج سلولیIntracellular pH - PH درون سلولیextracellular acidification - اسیدی شدن خارج سلولیOmeprazole - امپرازولbafilomycin A1 - بافیلومایسین A1Bioenergetic - بیو انرژیEwing sarcoma - سارکوما یوینگhypoxia-inducible factors - عوامل القایی هیپوکسیOxidative phosphorylation - فسفوریلاسیون اکسیداتیوPAS - نهperiodic acid-Schiff reaction - واکنش اسید-شیف فازheat shock protein 60 - پروتئین شوک حرارت 60glyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژنازGlycolysis - گلیکولیز یا قندکافت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: V-ATPase is a candidate therapeutic target for Ewing sarcoma V-ATPase is a candidate therapeutic target for Ewing sarcoma](/preview/png/8260841.png)
چکیده انگلیسی
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 far as candidate pathogenetic mechanisms. In this paper, we observed that ES cells simultaneously activate mitochondrial respiration and high levels of glycolysis. Moreover, although the most effective detoxification mechanism of proton intracellular storage is lysosomal compartmentalization, ES cells show a poorly represented lysosomal compartment, but a high sensitivity to the anti-lysosomal agent bafilomycin A1, targeting the V-ATPase proton pump. We therefore investigated the role of V-ATPase in the acidification activity of ES cells. ES cells with the highest GAPDH and V-ATPase expression also showed the highest acidification rate. Moreover, the localization of V-ATPase was both on the vacuolar and the plasma membrane of all ES cell lines. The acidic extracellular pH that we reproduced in vitro promoted high invasion ability and clonogenic efficiency. Finally, targeting V-ATPase with siRNA and omeprazole treatments, we obtained a significant selective reduction of tumor cell number. In summary, glycolytic activity and activation of V-ATPase are crucial mechanisms of survival of ES cells and can be considered as promising selective targets for the treatment of this tumor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1832, Issue 8, August 2013, Pages 1105-1116
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1832, Issue 8, August 2013, Pages 1105-1116
نویسندگان
Sofia Avnet, Gemma Di Pompo, Silvia Lemma, Manuela Salerno, Francesca Perut, Gloria Bonuccelli, Donatella Granchi, Nicoletta Zini, Nicola Baldini,