Evidence map›Paper›PMID 34192540›Full record

ArticleCell reports2021

Revealing molecular pathways for cancer cell fitness through a genetic screen of the cancer translatome.

Duygu Kuzuoglu-Ozturk, Zhiqiang Hu, Martina Rama, Emily Devericks, Jacob Weiss, Gary G Chiang, Stephen T Worland, Steven E Brenner, Hani Goodarzi, Luke A Gilbert and 1 more

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

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 14 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

11 authors at 2 institutions in 1 country.

Duygu Kuzuoglu-OzturkDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Zhiqiang HuDepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Martina RamaDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Emily DevericksDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Jacob WeissDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Gary G ChiangeFFECTOR Therapeutics, San Diego, CA 92121, USA.
Stephen T WorlandeFFECTOR Therapeutics, San Diego, CA 92121, USA.
Steven E BrennerDepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Hani GoodarziHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics and Department of Urology, University of California, San Francisco, San Francisco CA, 94158, USA.
Luke A GilbertDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Davide RuggeroDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: davide.ruggero@ucsf.edu.
University of California, San Francisco · USUniversity of California, Berkeley · US

Funding

Mechanisms of regulated translation control in cancer and its therapeutic implicationsR35CA242986 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUGGERO, DAVIDE · 2019 to 2025
$6.4M
Remodeling the translatome in N-myc mediated medulloblastoma and its therapeutic implicationsR01NS125668 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Davide Ruggero, WILLIAM A WEISS · 2022 to 2026
$3.3M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
NCI NIH HHS DP2 CA239597NCI NIH HHS R35 CA242986NINDS NIH HHS R01 NS125668
6 · The paper itself

Abstract

The major cap-binding protein eukaryotic translation initiation factor 4E (eIF4E), an ancient protein required for translation of all eukaryotic genomes, is a surprising yet potent oncogenic driver. The genetic interactions that maintain the oncogenic activity of this key translation factor remain unknown. In this study, we carry out a genome-wide CRISPRi screen wherein we identify more than 600 genetic interactions that sustain eIF4E oncogenic activity. Our data show that eIF4E controls the translation of Tfeb, a key executer of the autophagy response. This autophagy survival response is triggered by mitochondrial proteotoxic stress, which allows cancer cell survival. Our screen also reveals a functional interaction between eIF4E and a single anti-apoptotic factor, Bcl-xL, in tumor growth. Furthermore, we show that eIF4E and the exon-junction complex (EJC), which is involved in many steps of RNA metabolism, interact to control the migratory properties of cancer cells. Overall, we uncover several cancer-specific vulnerabilities that provide further resolution of the cancer translatome.

Indexed as

Genetic TestingProtein BiosynthesisSignal Transduction5' Untranslated RegionsAnimalsApoptosisAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbcl-X ProteinCell Line, TumorCell MovementCell ProliferationCRISPR-Cas SystemsEukaryotic Initiation Factor-4EExonsGenome, Human5' Untranslated RegionsBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbcl-X ProteinEukaryotic Initiation Factor-4EMetalloendopeptidasesMitochondrial ProteinsPeptide HydrolasesPMPCB protein, humanTFEB protein, humanautophagyBcl-xLcancerCRISPRieIF4EEJCmitochondriaTfebtranslation controlUPR(mt)-like stress response

Identifiers

PMID34192540
PMCPMC8323864
OpenAlexW3176279993

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.