Evidence map›Paper›PMID 31710966›Full record

ArticleiScience2019

HIF-mediated Suppression of DEPTOR Confers Resistance to mTOR Kinase Inhibition in Renal Cancer.

Hong Doan, Alexander Parsons, Shruthi Devkumar, Jogitha Selvarajah, Francesc Miralles, Veronica A Carroll

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

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Pharmacological inhibition of HIF2 protects against bone loss in an experimental model of estrogen deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

6 authors at 1 institution in 1 country.

Hong DoanVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK.
Alexander ParsonsVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK.
Shruthi DevkumarVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK; Centre for Biomedical Education, Institute of Medical and Biomedical Education, St George's, University of London, London SW17 0RE, UK.
Jogitha SelvarajahVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK; Centre for Biomedical Education, Institute of Medical and Biomedical Education, St George's, University of London, London SW17 0RE, UK.
Francesc MirallesVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK; Centre for Biomedical Education, Institute of Medical and Biomedical Education, St George's, University of London, London SW17 0RE, UK.
Veronica A CarrollVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK; Centre for Biomedical Education, Institute of Medical and Biomedical Education, St George's, University of London, London SW17 0RE, UK. Electronic address: vcarroll@sgul.ac.uk.
St George's, University of London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mechanistic target of rapamycin (mTOR) is a fundamental regulator of cell growth, proliferation, and metabolism. mTOR is activated in renal cancer and accelerates tumor progression. Here, we report that the mTOR inhibitor, DEP domain-containing mTOR-interacting protein (DEPTOR), is strikingly suppressed in clear cell renal cell carcinoma (ccRCC) tumors and cell lines. We demonstrate that DEPTOR is repressed by both hypoxia-inducible factors, HIF-1 and HIF-2, which occurs through activation of the HIF-target gene and transcriptional repressor, BHLHe40/DEC1/Stra13. Restoration of DEPTOR- and CRISPR/Cas9-mediated knockout experiments demonstrate that DEPTOR is growth inhibitory in ccRCC. Furthermore, loss of DEPTOR confers resistance to second-generation mTOR kinase inhibitors through deregulated mTORC1 feedback to IRS-2/PI3K/Akt. This work reveals a hitherto unknown mechanism of resistance to mTOR kinase targeted therapy that is mediated by HIF-dependent reprograming of mTOR/DEPTOR networks and suggests that restoration of DEPTOR in ccRCC will confer sensitivity to mTOR kinase therapeutics.

Indexed as

Biological SciencesCancerCell Biology

Identifiers

PMID31710966
PMCPMC6849413
OpenAlexW2981610289

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.