Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia.
Lise Willems,Lise Willems,Nathalie Jacque,Arnaud Jacquel,Nathalie Neveux,Thiago Trovati Maciel,Mireille Lambert,Alain Schmitt,Laury Poulain,Alexa S. Green,Madalina Uzunov,Olivier Kosmider,Olivier Kosmider,Isabelle Radford-Weiss,Ivan C. Moura,Patrick Auberger,Norbert Ifrah,Valérie Bardet,Valérie Bardet,Nicolas Chapuis,Nicolas Chapuis,Catherine Lacombe,Catherine Lacombe,Patrick Mayeux,Patrick Mayeux,Jerome Tamburini,Jerome Tamburini,Didier Bouscary,Didier Bouscary +28 more
Reads0
Chats0
TLDR
It is shown that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells, and that l-ases upregulate glutamine synthase expression in leukemic cells and that a GS knockdown enhances l-ase-induced apoptotic response in someAML cells.About:
This article is published in Blood.The article was published on 2013-11-14 and is currently open access. It has received 238 citations till now. The article focuses on the topics: Glutaminase & Glutamine.read more
Citations
More filters
Journal ArticleDOI
From Krebs to clinic: glutamine metabolism to cancer therapy.
TL;DR: An updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo is provided, and the recent potential applications of basic science discoveries in the clinical setting are explored.
Journal ArticleDOI
Metabolic control of cell death
TL;DR: The existence of several “metabolic checkpoints” is proposed, refined molecular mechanisms that sense a panel of metabolic variables and emit one or more signals controlling cell fate, which might allow for the development of novel pharmacological approaches that block or stimulate cell death by inducing specific metabolic alterations.
Journal ArticleDOI
ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer
M van Geldermalsen,M van Geldermalsen,Qian Wang,Qian Wang,Rajini Nagarajah,Rajini Nagarajah,Amy D. Marshall,Amy D. Marshall,Annora Thoeng,Annora Thoeng,Dadi Gao,Dadi Gao,William Ritchie,William Ritchie,Yue Feng,Yue Feng,Charles G. Bailey,Charles G. Bailey,Niantao Deng,Niantao Deng,Kate Harvey,Kate Harvey,Jane Beith,C.I. Selinger,Sandra A O'Toole,Sandra A O'Toole,Sandra A O'Toole,John E.J. Rasko,John E.J. Rasko,John E.J. Rasko,Jeff Holst,Jeff Holst +31 more
TL;DR: Preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer is provided, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of AsCT2, but also a marked reliance on its activity for sustained cellular proliferation.
Journal ArticleDOI
Glutamine Synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma
Saverio Tardito,Anais Oudin,Shafiq U. Ahmed,Fred Fack,Olivier Keunen,Liang Zheng,Hrvoje Miletic,Per Øystein Sakariassen,Adam Weinstock,Allon Wagner,Susan L. Lindsay,Andreas K. Hock,Susan C. Barnett,Eytan Ruppin,Svein H. Mørkve,Morten Lund-Johansen,Morten Lund-Johansen,Anthony J. Chalmers,Rolf Bjerkvig,Simone P. Niclou,Eyal Gottlieb +20 more
TL;DR: It is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation.
Journal ArticleDOI
Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion
Ji Zhang,Jing Fan,Sriram Venneti,Justin R. Cross,Toshimitsu Takagi,Bhavneet Bhinder,Hakim Djaballah,Masayuki Kanai,Emily H. Cheng,Alexander R. Judkins,Bruce R. Pawel,Julie E. Baggs,Sara Cherry,Joshua D. Rabinowitz,Craig B. Thompson +14 more
TL;DR: It was found that asparagine was necessary and sufficient to suppress glutamine-withdrawal-induced apoptosis without restoring the levels of other nonessential amino acids or TCA cycle intermediates.
References
More filters
mTOR Signaling in Growth Control and Disease
TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Journal ArticleDOI
mTOR signaling in growth control and disease.
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
TL;DR: It is argued that altered metabolism has attained the status of a core hallmark of cancer.
Journal ArticleDOI
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Yasemin Sancak,Timothy R. Peterson,Yoav D. Shaul,Robert A. Lindquist,Carson C. Thoreen,Liron Bar-Peled,David M. Sabatini,David M. Sabatini +7 more
TL;DR: It is found that the Rag proteins—a family of four related small guanosine triphosphatases (GTPases)—interact with mTORC1 in an amino acid–sensitive manner and are necessary for the activation of the m TORC1 pathway by amino acids.
Journal ArticleDOI
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids
Yasemin Sancak,Liron Bar-Peled,Roberto Zoncu,Andrew L. Markhard,Shigeyuki Nada,David M. Sabatini +5 more
TL;DR: It is shown that amino acids induce the movement of m TORC1 to lysosomal membranes, where the Rag proteins reside, and Rag-Ragulator-mediated translocation of mTORC1 is the key event in amino acid signaling to mtorC1.
Related Papers (5)
Antitumor Activity of the Glutaminase Inhibitor CB-839 in Triple-Negative Breast Cancer
Matthew I. Gross,Susan Demo,Jennifer B. Dennison,Lijing Chen,Tania Chernov-Rogan,Bindu Goyal,Julie Janes,Guy J. Laidig,Evan R. Lewis,Jim Li,Andrew L. Mackinnon,Francesco Parlati,Mirna Rodriguez,Peter Shwonek,Eric Brian Sjogren,Timothy Friend Stanton,Taotao Wang,Jinfu Yang,Frances Zhao,Mark K. Bennett +19 more