Evidence map›Paper›PMID 32427827›Full record

ArticleNature communications2020

Translational control of breast cancer plasticity.

Michael Jewer, Laura Lee, Matthew Leibovitch, Guihua Zhang, Jiahui Liu, Scott D Findlay, Krista M Vincent, Kristofferson Tandoc, Dylan Dieters-Castator, Daniela F Quail and 14 more

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

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
6.5field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.

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

16 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

24 authors at 6 institutions in 3 countries.

Michael JewerDepartment of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
Laura LeeDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Matthew LeibovitchLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Guihua ZhangDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Jiahui LiuDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Scott D FindlayDepartment of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
Krista M VincentDepartment of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
Kristofferson TandocLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Dylan Dieters-CastatorDepartment of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
Daniela F QuailGoodman Cancer Center, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-6969-3250
Indrani DuttaDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Mackenzie CoathamDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Zhihua XuDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Aakshi PuriLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Bo-Jhih GuanDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Maria HatzoglouDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Andrea BrumwellDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
James UniackeDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.ORCID http://orcid.org/0000-0001-9632-4277
Christos PatsisLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Antonis KoromilasLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Julia SchuelerCharles River Discovery Research Services Germany, Freiburg, Germany.ORCID http://orcid.org/0000-0003-1984-7343
Gabrielle M SiegersDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.ORCID http://orcid.org/0000-0003-2154-0279
Ivan TopisirovicLady Davis Institute, Departments of Oncology and Biochemistry, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-5510-9762
Lynne-Marie PostovitDepartment of Oncology, University of Alberta, Edmonton, AB, Canada. l.postovit@queensu.ca.ORCID http://orcid.org/0000-0002-8088-4197
University of Alberta · CAMcGill University · CAWestern University · CACase Western Reserve University · USUniversity of Guelph · CACharles River Laboratories (Germany) · DE

Funding

Regulation of Gene Expression During StressR01DK053307 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI HATZOGLOU, MARIA · 1998 to 2021
$9.6M
Translational Control by Osmotically Active SolutesR37DK060596 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI HATZOGLOU, MARIA · 2011 to 2020
$5.3M
NIDDK NIH HHS R01 DK053307NIDDK NIH HHS R37 DK060596
6 · The paper itself

Abstract

Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast cancer cells NANOG, SNAIL and NODAL transcripts manifest multiple isoforms characterized by different 5' Untranslated Regions (5'UTRs), whereby translation of a subset of these isoforms is stimulated under hypoxia. The accumulation of the corresponding proteins induces plasticity and "fate-switching" toward stem cell-like phenotypes. Mechanistically, we observe that mTOR inhibitors and chemotherapeutics induce translational activation of a subset of NANOG, SNAIL and NODAL mRNA isoforms akin to hypoxia, engendering stem-cell-like phenotypes. These effects are overcome with drugs that antagonize translational reprogramming caused by eIF2α phosphorylation (e.g. ISRIB), suggesting that the Integrated Stress Response drives breast cancer plasticity. Collectively, our findings reveal a mechanism of induction of plasticity of breast cancer cells and provide a molecular basis for therapeutic strategies aimed at overcoming drug resistance and abrogating metastasis.

Indexed as

5' Untranslated RegionsAntineoplastic AgentsBreast NeoplasmsCell HypoxiaCell Line, TumorEukaryotic Initiation Factor-2FemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsNanog Homeobox ProteinNodal ProteinPhosphorylationProtein BiosynthesisRNA IsoformsSnail Family Transcription Factors5' Untranslated RegionsAntineoplastic AgentsEukaryotic Initiation Factor-2Nanog Homeobox ProteinNodal ProteinRNA IsoformsSNAI1 protein, humanSnail Family Transcription Factors

Identifiers

PMID32427827
PMCPMC7237473
OpenAlexW3026944009

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.