Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy
Δημιουργός/Συγγραφέας:	Mitra, Devina Vega-Rubin-de-Celis, Silvia Royla, Nadine Bernhardt, Stephan Wilhelm, Heike Tarade, Nooraldeen Poschet, Gernot Buettner, Michael Binenbaum, Ilona Borgoni, Simone Vetter, Martina Kantelhardt, Eva Johanna Thomssen, Christoph [EL] Χατζηιωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis Hell, Rüdiger Kempa, Stefan Müller-Decker, Karin Wiemann, Stefan
Εκδότης:	Wiley
Ημερομηνία:	2021-04-15
Γλώσσα:	Αγγλικά
ISSN:	0020-7136 1097-0215
DOI:	10.1002/ijc.33456
Άλλο:	33368291
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	International journal of cancer
Τόμος/Κεφάλαιο:	148
Τεύχος:	8
Σελίδες:	1993-2009
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Κυτταρολογία[EN] Cytology [EL] Βιοχημεία[EN] Biochemistry [EL] Βιοπληροφορική[EN] Bioinformatics
Λέξεις-Κλειδιά:	GPT2 Autophagy Breast cancer Cancer metabolism mTORC1 Animals Autophagy CRISPR-Cas Systems Cell Line, Tumor Female Gene Knockout Techniques Humans MCF-7 Cells Mice, Inbred NOD Mice, Knockout Mice, SCID RNA Interference Survival Analysis Transaminases Triple Negative Breast Neoplasms Tumor Burden Xenograft Model Antitumor Assays Gene Expression Regulation, Neoplastic
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://onlinelibrary.wiley.com/doi/10.1002/ijc.33456
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://onlinelibrary.wiley.com/journal/10970215
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο