Evidence map›Paper›PMID 24747441›Full record

ArticleNature cell biology2014

An integrin β₃-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition.

Laetitia Seguin, Shumei Kato, Aleksandra Franovic, M Fernanda Camargo, Jacqueline Lesperance, Kathryn C Elliott, Mayra Yebra, Ainhoa Mielgo, Andrew M Lowy, Hatim Husain and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed, 2 pooled it
21.4field-weighted citation impact, top 1% 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

254 citing papers in PubMed, 2 syntheses or guidelines pooled it, 370 citations in OpenAlex.

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  12. Selective targeting of NRF2-high pancreatic ductal adenocarcinoma with an NQO1-activatable prodrug.Proceedings of the National Academy of Sciences of the United States of America · 2026
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194 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 1 country.

Laetitia SeguinDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Shumei KatoSchool of Medicine, Division of Hematology/Oncology, University of California, San Diego, La Jolla, California 92093, USA.
Aleksandra FranovicDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
M Fernanda CamargoDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Jacqueline LesperanceDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Kathryn C ElliottDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Mayra YebraDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Ainhoa MielgoDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Andrew M LowyDivision of Surgical Oncology, Departments of Surgery, San Diego, La Jolla, California 92093, USA.
Hatim HusainSchool of Medicine, Division of Hematology/Oncology, University of California, San Diego, La Jolla, California 92093, USA.
Tina CasconeDepartments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Lixia DiaoDepartments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jing WangDepartments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ignacio I WistubaDepartments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
John V HeymachDepartments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Scott M LippmanMoores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Jay S DesgrosellierDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Sudarshan AnandDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Sara M WeisDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
David A ChereshDepartment of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
University of California, San Diego · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
TYROSINE KINASE C-ABL AND BCR-ABL IN INTEGRIN DEPENDENT SIGNALINGP01HL057900 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHATTIL, SANFORD J · 1997 to 2012
$17.4M
UCSD Cancer Center Training Program in Drug DevelopmentT32CA121938 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Bouvet, Dwayne G. Stupack · 2006 to 2026
$10.3M
REGULATION OF TUMOR CELL ATTACHMENT BY SURFACE ANTIGENSR01CA045726 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 1988 to 2017
$7.4M
VEGF and PDGF in angiogenesis and tumor progressionR37CA050286 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 1999 to 2013
$6.3M
RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
Targeting a non-canonical RAS-driven pathway in pancreatic cancerR01CA168692 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 2012 to 2016
$1.6M
MicroRNA Regulation Of Cell Survival In Angiogenesis & Vessel MaturationR00HL112962 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ANAND, SUDARSHAN · 2014 to 2016
$733k
NCI NIH HHS CA155620NCI NIH HHS CA168692NCI NIH HHS CA45726NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA045726NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA168692NCI NIH HHS R37 CA050286NCI NIH HHS T32 CA121938NCI NIH HHS T32CA121938NHLBI NIH HHS HL57900NHLBI NIH HHS P01 HL057900NHLBI NIH HHS R00 HL112962PHS HHS R3750286
6 · The paper itself

Abstract

Tumour cells, with stem-like properties, are highly aggressive and often show drug resistance. Here, we reveal that integrin α(v)β₃ serves as a marker of breast, lung and pancreatic carcinomas with stem-like properties that are highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This was observed in vitro and in mice bearing patient-derived tumour xenografts or in clinical specimens from lung cancer patients who had progressed on erlotinib. Mechanistically, α(v)β₃, in the unliganded state, recruits KRAS and RalB to the tumour cell plasma membrane, leading to the activation of TBK1 and NF-κB. In fact, α(v)β₃ expression and the resulting KRAS-RalB-NF-κB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance. Pharmacological targeting of this pathway with bortezomib reversed both tumour stemness and erlotinib resistance. These findings not only identify α(v)β₃ as a marker/driver of carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to RTK inhibition.

Indexed as

Drug Resistance, NeoplasmAnimalsCell Line, TumorCell ProliferationClinical Trials, Phase II as TopicErbB ReceptorsErlotinib HydrochlorideFemaleHumansIntegrin alphaVbeta3Integrin beta3Lung NeoplasmsMiceMice, Inbred NODMice, NudeMice, SCIDEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideIntegrin alphaVbeta3Integrin beta3ITGB3 protein, humanKRAS protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-relProto-Oncogene Proteins p21(ras)QuinazolinesRalb protein, humanral GTP-Binding Proteinsras ProteinsTBK1 protein, human

Identifiers

PMID24747441
PMCPMC4105198
OpenAlexW2029572050

What OpenQuestion holds

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Registered trials

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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.