Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism.
Maša Ždralević,Almut Brand,Lorenza Di Ianni,Katja Dettmer,Jörg Reinders,Katrin Singer,K. Peter,Annette Schnell,Christina Bruss,Sonja-Maria Decking,Gudrun E. Koehl,Blanca Felipe-Abrio,Jérôme Durivault,Pascale Bayer,Marie Evangelista,Thomas O'Brien,Peter J. Oefner,Kathrin Renner,Jacques Pouysségur,Marina Kreutz,Marina Kreutz +20 more
TLDR
It is demonstrated that the Warburg effect is not only based on high LDHA expression, as both LDHA and LDHB need to be deleted to suppress fermentative glycolysis, and that the metabolic shift to OXPHOS caused by LDHA/B genetic disruptions is responsible for the tumors' escape and growth.About:
This article is published in Journal of Biological Chemistry.The article was published on 2018-10-12 and is currently open access. It has received 126 citations till now. The article focuses on the topics: Lactate dehydrogenase A & Lactate dehydrogenase.read more
Citations
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Mitochondrial Metabolism as a Target for Cancer Therapy.
TL;DR: The rationale of using these anti-cancer agents in clinical trials and how to effectively utilize them in different tumor contexts are discussed.
Journal ArticleDOI
Mitochondrial DNA copy number in human disease: the more the better?
Roberta Filograna,Roberta Filograna,Mara Mennuni,Mara Mennuni,David Alsina,David Alsina,Nils-Göran Larsson,Nils-Göran Larsson +7 more
TL;DR: Current knowledge of the role of mtDNA copy number regulation in various types of human diseases, including mitochondrial disorders, neurodegenerative disorders and cancer, and during ageing is critically discussed.
Journal ArticleDOI
Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy.
Kathrin Renner,Christina Bruss,Annette Schnell,Gudrun E. Koehl,Holger M. Becker,Matthias Fante,Ayse Nur Menevse,Nathalie Kauer,Raquel Blazquez,Lisa Hacker,Sonja Maria Decking,Toszka Bohn,Stephanie Faerber,Katja Evert,Lisa Aigle,Sabine Amslinger,Maria Landa,Oscar Krijgsman,Elisa A. Rozeman,Christina Brummer,Peter J. Siska,Katrin Singer,Stefanie Pektor,Matthias Miederer,Katrin Peter,Eva Gottfried,Wolfgang Herr,Ibtisam Marchiq,Jacques Pouysségur,William R. Roush,SuFey Ong,Sarah Warren,Tobias Pukrop,Philipp Beckhove,Sven A. Lang,Tobias Bopp,Christian U. Blank,John L. Cleveland,Peter J. Oefner,Katja Dettmer,Mark J. Selby,Marina Kreutz +41 more
TL;DR: It is reported that melanoma patients with high expression of glycolysis-related genes show a worse progression free survival upon anti-PD1 treatment, and this findings support the rationale for targeting Glycolytic tumors together with checkpoint inhibitors in clinical trials.
Journal ArticleDOI
Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment.
TL;DR: The role of small molecule inhibitors in targeting LDH activity is highlighted and the development of safer and more effective LDH inhibitors are emphasized and generated interest in designing combination therapies based on LDH inhibition.
Journal ArticleDOI
LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis
Manoj Arra,Gaurav Swarnkar,Ke Ke,Jesse E. Otero,Jun Ying,Xin Duan,Takashi Maruyama,Muhammad Farooq Rai,Regis J. O'Keefe,Gabriel Mbalaviele,Jie Shen,Yousef Abu-Amer,Yousef Abu-Amer +12 more
TL;DR: It is shown that inflammatory NF-κB signalling drives a glycolytic shift in chondrocytes and the production of ROS, which drives cartilage catabolism, which identifies LDHA as a potential therapeutic target for OA treatment.
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