Evidence map›Paper›PMID 35626002›Full record

ArticleCancers2022

Frequent 4EBP1 Amplification Induces Synthetic Dependence on FGFR Signaling in Cancer.

Prathibha Mohan, Joyce Pasion, Giovanni Ciriello, Nathalie Lailler, Elisa de Stanchina, Agnes Viale, Anke van den Berg, Arjan Diepstra, Hans-Guido Wendel, Viraj R Sanghvi and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 49% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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 5 institutions in 3 countries.

Prathibha MohanCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Joyce PasionCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Giovanni CirielloDepartment of Computational Biology, University of Lausanne, CH-1005 Lausanne, Switzerland.
Nathalie LaillerIntegrated Genomics Operation, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elisa de StanchinaMolecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Agnes VialeIntegrated Genomics Operation, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Anke van den BergDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0002-8894-2638
Arjan DiepstraDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0001-9239-1050
Hans-Guido WendelCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Viraj R SanghviDepartment of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.ORCID 0000-0001-6526-7820
Kamini SinghDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Albert Einstein Cancer Center, Bronx, NY 10461, USA.
Memorial Sloan Kettering Cancer Center · USUniversity Medical Center Groningen · NLAlbert Einstein College of Medicine · USUniversity of Lausanne · CHUniversity of Miami · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Targeting Oncogenic Pathways in Genetically Complex SarcomasP50CA217694 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Marc Ladanyi · 2018 to 2026
$21.5M
Translating Stress Response Targeted Therapy for B-Cell LymphomasP50CA192937 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ZELENETZ, ANDREW D. · 2016 to 2020
$10.9M
Towards targeting the lymphoma microenvironmentR35CA252982 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Hans-Guido Wendel · 2020 to 2026
$6.2M
The genomic pathogenesis of Follicular LymphomaR01CA190384 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MALEK, SAMI NIMER, WENDEL, HANS-GUIDO · 2015 to 2019
$2.7M
Towards The Chemotherapy-Free Treatment of Follicular LymphomaR01CA183876 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI WENDEL, HANS-GUIDO · 2014 to 2018
$2.5M
Exploring oncogenic translation programs in cancerR01CA207217 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI WENDEL, HANS-GUIDO · 2016 to 2020
$2.1M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA192937NCI NIH HHS P50 CA217694NCI NIH HHS R01 CA183876NCI NIH HHS R01 CA190384NCI NIH HHS R01 CA207217NCI NIH HHS R35 CA252982
6 · The paper itself

Abstract

The eIF4E translation initiation factor has oncogenic properties and concordantly, the inhibitory eIF4E-binding protein (4EBP1) is considered a tumor suppressor. The exact molecular effects of 4EBP1 activation in cancer are still unknown. Surprisingly, 4EBP1 is a target of genomic copy number gains (Chr. 8p11) in breast and lung cancer. We noticed that 4EBP1 gains are genetically linked to gains in neighboring genes, including WHSC1L1 and FGFR1. Our results show that FGFR1 gains act to attenuate the function of 4EBP1 via PI3K-mediated phosphorylation at Thr37/46, Ser65, and Thr70 sites. This implies that not 4EBP1 but instead FGFR1 is the genetic target of Chr. 8p11 gains in breast and lung cancer. Accordingly, these tumors show increased sensitivity to FGFR1 and PI3K inhibition, and this is a therapeutic vulnerability through restoring the tumor-suppressive function of 4EBP1. Ribosome profiling reveals genes involved in insulin signaling, glucose metabolism, and the inositol pathway to be the relevant translational targets of 4EBP1. These mRNAs are among the top 200 translation targets and are highly enriched for structure and sequence motifs in their 5'UTR, which depends on the 4EBP1-EIF4E activity. In summary, we identified the translational targets of 4EBP1-EIF4E that facilitate the tumor suppressor function of 4EBP1 in cancer.

Indexed as

4EBP1breast cancereIF4EFGFR1lung cancerribosome footprinting

Identifiers

PMID35626002
PMCPMC9139685
OpenAlexW4280563149

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.