Evidence mapPaperPMID 37014850Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

eIF2Bδ blocks the integrated stress response and maintains eIF2B activity and cancer metastasis by overexpression in breast cancer stem cells.

Malavika Gupta, Beth A Walters, Olga Katsara, Karol Granados Blanco, Phillip A Geter, Robert J Schneider

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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.

Malavika GuptaDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.
Beth A WaltersDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.
Olga KatsaraDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.
Karol Granados BlancoDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.
Phillip A GeterDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.
Robert J SchneiderDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016.ORCID 0000-0001-5807-5564
New York University · US

Funding

Tumor Immunology (TIM) Research ProgramP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 1985 to 2025
$21.1M
TRAINING PROGRAM IN MOLECULAR ONCOLOGY &IMMUNOLOGYT32CA009161 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 1985 to 2005
$3.9M
Training in Pharmacological SciencesT32GM066704 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2004 to 2005
$221k
NCATS NIH HHS UL1 TR000038NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA178509NCI NIH HHS R01 CA248397NCI NIH HHS T32 CA009161NIGMS NIH HHS T32 GM066704
6 · The paper itself

Abstract

Breast cancer (BC) metastasis involves cancer stem cells (CSCs) and their regulation by micro-RNAs (miRs), but miR targeting of the translation machinery in CSCs is poorly explored. We therefore screened miR expression levels in a range of BC cell lines, comparing non-CSCs to CSCs, and focused on miRs that target translation and protein synthesis factors. We describe a unique translation regulatory axis enacted by reduced expression of miR-183 in breast CSCs, which we show targets the eIF2Bδ subunit of guanine nucleotide exchange factor eIF2B, a regulator of protein synthesis and the integrated stress response (ISR) pathway. We report that reduced expression of miR-183 greatly increases eIF2Bδ protein levels, preventing strong induction of the ISR and eIF2α phosphorylation, by preferential interaction with P-eIF2α. eIF2Bδ overexpression is essential for BC cell invasion, metastasis, maintenance of metastases, and breast CSC expansion in animal models. Increased expression of eIF2Bδ, a site of action of the drug ISRIB that also prevents ISR signaling, is essential for breast CSC maintenance and metastatic capacity.

Indexed as

MicroRNAsNeoplasmsAnimalsEukaryotic Initiation Factor-2BGuanine Nucleotide Exchange FactorsNeoplastic Stem CellsEukaryotic Initiation Factor-2BGuanine Nucleotide Exchange FactorsMicroRNAsbreast cancerintegrated stress responsemetastasistranslational regulationunfolded protein response

Identifiers

PMID37014850
PMCPMC10104532
OpenAlexW4362523254

What Socratic 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 Socratic graph.