7th Scientific Meeting of the Japanese Society of Anti-Aging Medicine / with Meeting Report by T. Yoshikawa
Year: 2007
Type: article
Abstract: Aims: Enhanced glycolysis even less than 20% oxygen condition is the characteristic property of most cancer cells, called the Warburg effect.It is exploited clinically in detection of primary tumors and metastasis based on positron emission tomography measurement of 2-[18F] fluoro-2-deoxy-D-glucose uptake, suggesting undisputed significance of the Warburg effect in cancer.However, there have been few mechanistic insights into its relationship with the well-characterized molecular and genetic events associated with cellular immortalization.Methods and Results: Through an unbiased screen for genes that can immortalize mouse embryonic fibroblasts (MEFs), we identified the glycolytic enzyme phosphoglycerate mutase (PGM).A twofold increase in PGM activity enhances glycolytic flux, allows indefinite proliferation of primary MEFs.Glucosephosphate isomerase (GPI), another glycolytic enzyme, displays similar activity and conversely depletion of PGM or GPI triggers premature senescence.Immortalized MEFs and mouse embryonic stem cells (ES cells) display higher glycolytic flux with reduced oxygen consumption, and more resistance to oxidative damage than senescent cells.These metabolic property might support the proliferative potential of ES cells, proven by the inhibition of its self-renewality or glycolytic flux.Finally we found molecular link between p53 axis and PGM.As wild-type p53 down-regulates PGM, mutation of p53 can facilitate immortalization via effects on PGM levels and glycolysis. Conclusions:We discovered unexpected aspect of the Warburg effect, protecting cells from senescence effect of oxidative damage in primary cells and ES cells.
DOI: 10.1159/000110786
Authors: Györgyi Arató, D.A. de Luis, M. Gonzalez Sagrado, R. Conde, R. Aller, O. Izaola, E. Romero, Berthold Koletzko, Andreja Širca-Čampa, Primož Kotnik, Mirjana Zupančič, Tadej Battelino, Ciril Križišnik, Lajos Biró, Andrea Regöly-Mérei, Katalin Nagy, Szabolcs Péter, M.V. Aguilar, P. Saavedra, F.J. Arrieta, C.J. Mateos, M.J. González, I. Meseguer, M.C. Martínez-Para, Toshikazu Yoshikawa, Jean-Claude Pineau, Anne-Marie Guihard-Costa, Christine Boesch-Saadatmandi, Erika Most, Edgar Weigand, Michel Bocquet, B. Strasser, A. Spreitzer, P. Haber, António Guerra, Hans Demmelmair, André Michael Toschke, Csaba Szabó, Éva Martos, Magda Antal, P. Marhol, P. Dlouhý, J. Rambousková, R. Pokorný, O. Wiererová, D. Hrnčířová, B. Procházka, M. Anděl, Ilia Volkov, Inna Rudoy, Mochamed Machagna, Inna Glezer, Uri Ganel, Anna Orenshtein, Yan Press, D. Papandreou, M. Stamou, P. Malindretos, I. Rousso, I. Mavromichalis, K. Subhash C. Bose, B.K. Agrawal, José E. Galgani, Carolina A. Aguirre, Ricardo D. Uauy, Erik O. Díaz, Matevž Štimec, Nataša Fidler Mis, Katarina Smole, Szabolcs Péter, Andrea Regöly-Mérei, Lajos Biró, Katalin Nagy, Györgyi Arató, Csaba Szabó, Adrienn Vámos, Éva Martos, Magda Antal
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2593620324