Evidence map›Paper›PMID 20498635›Full record

ArticleOncogene2010

Proton-assisted amino-acid transporters are conserved regulators of proliferation and amino-acid-dependent mTORC1 activation.

S Heublein, S Kazi, M H Ogmundsdóttir, E V Attwood, S Kala, C A R Boyd, C Wilson, D C I Goberdhan

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 140 citations in OpenAlex.

  1. Trial
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  8. Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness.International journal of molecular sciences · 2022
    Review
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  10. Effects of Dietary Chlorogenic Acid Supplementation Derived fromOxidative medicine and cellular longevity · 2022
    Article
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12 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

8 authors at 1 institution in 1 country.

S HeubleinDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
S Kazi
M H Ogmundsdóttir
E V Attwood
S Kala
C A R Boyd
C Wilson
D C I Goberdhan
University of Oxford · GB

Funding

Cancer Research UK A6174Cancer Research UK A6181Cancer Research UK A9093Cancer Research UK C19591/A9093Cancer Research UK C7713/A6174CIHR C191591/A6181
6 · The paper itself

Abstract

The phosphoinositide3-kinase (PI3K)/Akt and downstream mammalian target of rapamycin complex 1 (mTORC1) signalling cascades promote normal growth and are frequently hyperactivated in tumour cells. mTORC1 is also regulated by local nutrients, particularly amino acids, but the mechanisms involved are poorly understood. Unexpectedly, members of the proton-assisted amino-acid transporter (PAT or SLC36) family emerged from in vivo genetic screens in Drosophila as transporters with uniquely potent effects on mTORC1-mediated growth. In this study, we show the two human PATs that are widely expressed in normal tissues and cancer cell lines, namely PAT1 and PAT4, behave similarly to fly PATs when expressed in Drosophila. Small interfering RNA knockdown shows that these molecules are required for the activation of mTORC1 targets and for proliferation in human MCF-7 breast cancer and HEK-293 embryonic kidney cell lines. Furthermore, activation of mTORC1 in starved HEK-293 cells stimulated by amino acids requires PAT1 and PAT4, and is elevated in PAT1-overexpressing cells. Importantly, in HEK-293 cells, PAT1 is highly concentrated in intracellular compartments, including endosomes, wherein mTOR shuttles upon amino-acid stimulation. Therefore our data are consistent with a model in which PATs modulate the activity of mTORC1 not by transporting amino acids into the cell but by modulating the intracellular response to amino acids.

Indexed as

Cell ProliferationAmino AcidsAmino Acid Transport SystemsCell Line, TumorHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesProteinsProtonsTOR Serine-Threonine KinasesTranscription FactorsAmino AcidsAmino Acid Transport SystemsMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesProteinsProtonsTOR Serine-Threonine KinasesTranscription Factors

Identifiers

PMID20498635
PMCPMC3018277
OpenAlexW2065642231

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.