Evidence map›Paper›PMID 28648777›Full record

ArticleMolecular cell2017

mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT.

Yuchao Gu, Claudio P Albuquerque, Daniel Braas, Wei Zhang, Genaro R Villa, Junfeng Bi, Shiro Ikegami, Kenta Masui, Beatrice Gini, Huijun Yang and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 1 pooled it
9.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

141 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

81 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 2 countries.

Yuchao GuDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Claudio P AlbuquerqueLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Daniel BraasDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, Los Angeles, CA 90095, USA.
Wei ZhangDepartment of Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA.
Genaro R VillaDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Medical Scientist Training Program, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Junfeng BiLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Shiro IkegamiDivision of Neurological Surgery, Chiba Cancer Center, Chiba 260-8717, Japan.
Kenta MasuiDepartment of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Beatrice GiniDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Huijun YangLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Timothy C GahmanSmall Molecule Discovery Program, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Andrew K ShiauSmall Molecule Discovery Program, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Timothy F CloughesyDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Heather R ChristofkDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, Los Angeles, CA 90095, USA.
Huilin ZhouLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093 USA.
Kun-Liang GuanDepartment of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093 USA.
Paul S MischelLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pathology, UCSD School of Medicine, La Jolla, CA 92093 USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093 USA. Electronic address: pmischel@ucsd.edu.
University of California, Los Angeles · USLudwig Cancer Research · USUniversity of California, San Diego · USChiba Cancer Center · JPMoores Cancer CenterTokyo Women's Medical University · JPUniversity of California, San Francisco · US

Funding

PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONR01GM051586 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROWN, JOAN HELLER · 1994 to 2024
$7.9M
The mTOR and Hippo pathway in cell growth and cancerR35CA196878 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUAN, KUN-LIANG · 2015 to 2019
$4.0M
The role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4M
Suppression of duplication-mediated genome rearrangements by protein sumoylationR01GM116897 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHOU, HUILIN · 2015 to 2023
$2.6M
A Novel Approach to Treating Glioblastoma through Activation of the Liver X RecepF31CA186668 · NCI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI VILLA, GENARO R. · 2014 to 2016
$104k
NCI NIH HHS F31 CA186668NCI NIH HHS R35 CA196878NIGMS NIH HHS R01 GM051586NIGMS NIH HHS R01 GM116897NINDS NIH HHS R01 NS073831
6 · The paper itself

Abstract

Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism regulating amino acid metabolism in cancer, enabling tumor cells to adapt to changing environmental conditions.

Indexed as

A549 CellsAmino Acid Transport System y+Brain NeoplasmsCysteineGlioblastomaGlutamineGlutathioneHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationPhosphorylationProtein BindingProteomicsRNA InterferenceAmino Acid Transport System y+CysteineGlutamineGlutathioneMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesSerineSLC7A11 protein, humanTOR Serine-Threonine Kinasescancerglioblastomaglutamate metabolismglutathione metabolismmTORC2xCT

Identifiers

PMID28648777
PMCPMC5521991
OpenAlexW2690859775

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.