@article{3102529,
    title = "Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy",
    author = "Mitra, D. and Vega-Rubin-de-Celis, S. and Royla, N. and Bernhardt, S. and Wilhelm, H. and Tarade, N. and Poschet, G. and Buettner, M. and Binenbaum, I. and Borgoni, S. and Vetter, M. and Kantelhardt, E.J. and Thomssen, C. and Chatziioannou, A. and Hell, R. and Kempa, S. and Müller-Decker, K. and Wiemann, S.",
    journal = "International Journal  of Cancer",
    year = "2021",
    volume = "148",
    number = "8",
    pages = "1993-2009",
    publisher = "Wiley-Liss, Inc.",
    issn = "0020-7136",
    doi = "10.1002/ijc.33456",
    keywords = "alanine;  alanine aminotransferase;  glucose;  glutamate pyruvate transaminase 2;  glutamine;  lactic acid;  mammalian target of rapamycin complex 1;  small interfering RNA;  unclassified drug;  aminotransferase;  GPT2 protein, human, antineoplastic activity;  Article;  autophagy (cellular);  carcinogenesis;  cell proliferation;  citric acid cycle;  CRISPR-CAS9 system;  gene expression profiling;  gene targeting;  glucose metabolism;  glutaminolysis;  glycolysis;  human;  human cell;  human tissue;  immunoblotting;  in vivo study;  isotope labeling;  mass fragmentography;  microarray analysis;  multicenter study;  protein depletion;  protein expression;  protein function;  protein targeting;  real time polymerase chain reaction;  triple negative breast cancer;  upregulation;  animal;  autophagy;  CRISPR Cas system;  drug screening;  female;  gene expression regulation;  gene knockout;  genetics;  knockout mouse;  MCF-7 cell line;  metabolism;  nonobese diabetic mouse;  procedures;  RNA interference;  SCID mouse;  survival analysis;  triple negative breast cancer;  tumor cell line;  tumor volume, Animals;  Autophagy;  Cell Line, Tumor;  CRISPR-Cas Systems;  Female;  Gene Expression Regulation, Neoplastic;  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",
    abstract = "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. © 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC."
}