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Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy

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Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy
Wiemann, Stefan
Müller-Decker, Karin
Royla, Nadine
Tarade, Nooraldeen
Buettner, Michael
Poschet, Gernot
Kantelhardt, Eva Johanna
Vega-Rubin-de-Celis, Silvia
Bernhardt, Stephan
Hell, Rüdiger
Mitra, Devina
Vetter, Martina
Wilhelm, Heike
Borgoni, Simone
Binenbaum, Ilona
Thomssen, Christoph
Χατζηιωάννου, Αριστοτέλης
Kempa, Stefan
Άρθρο σε επιστημονικό περιοδικό
2021-04-15
Uncontrolled proliferation and altered metabolic reprogramming are hallmarks of cancer. Active glycolysis and glutaminolysis are characteristic features of these hallmarks and required for tumorigenesis. A fine balance between cancer metabolism and autophagy is a prerequisite of homeostasis within cancer cells. Here we show that glutamate pyruvate transaminase 2 (GPT2), which serves as a pivot between glycolysis and glutaminolysis, is highly upregulated in aggressive breast cancers, particularly the triple-negative breast cancer subtype. Abrogation of this enzyme results in decreased tricarboxylic acid cycle intermediates, which promotes the rewiring of glucose carbon atoms and alterations in nutrient levels. Concordantly, loss of GPT2 results in an impairment of mechanistic target of rapamycin complex 1 activity as well as the induction of autophagy. Furthermore, in vivo xenograft studies have shown that autophagy induction correlates with decreased tumor growth and that markers of induced autophagy correlate with low GPT2 levels in patient samples. Taken together, these findings indicate that cancer cells have a close network between metabolic and nutrient sensing pathways necessary to sustain tumorigenesis and that aminotransferase reactions play an important role in maintaining this balance.
Κυτταρολογία (EL)
Βιοχημεία (EL)
Βιοπληροφορική (EL)
Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες) (EL)
Cytology (EN)
Biochemistry (EN)
Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) (EN)
Bioinformatics (EN)
Triple Negative Breast Neoplasms (EN)
GPT2 (EN)
Humans (EN)
Gene Expression Regulation, Neoplastic (EN)
Breast cancer (EN)
Tumor Burden (EN)
Gene Knockout Techniques (EN)
Mice, SCID (EN)
Autophagy (EN)
Mice, Knockout (EN)
Xenograft Model Antitumor Assays (EN)
Animals (EN)
Cancer metabolism (EN)
MCF-7 Cells (EN)
RNA Interference (EN)
Transaminases (EN)
CRISPR-Cas Systems (EN)
Survival Analysis (EN)
Cell Line, Tumor (EN)
Female (EN)
Mice, Inbred NOD (EN)
mTORC1 (EN)
English
Wiley
International journal of cancer
Copyright © 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.el
National Hellenic Research Foundation (NHRF)
Helios - Repository of the National Hellenic Research Foundation (NHRF)



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