Evidence map›Paper›PMID 32265225›Full record

ArticleCancer research2020

IRE1α Disruption in Triple-Negative Breast Cancer Cooperates with Antiangiogenic Therapy by Reversing ER Stress Adaptation and Remodeling the Tumor Microenvironment.

Jonathan M Harnoss, Adrien Le Thomas, Mike Reichelt, Ofer Guttman, Thomas D Wu, Scot A Marsters, Anna Shemorry, David A Lawrence, David Kan, Ehud Segal and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

72 citing papers in PubMed, 84 citations in OpenAlex.

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12 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

21 authors at 5 institutions in 1 country.

Jonathan M HarnossCancer Immunology, Genentech, Inc., South San Francisco, California.
Adrien Le ThomasCancer Immunology, Genentech, Inc., South San Francisco, California.
Mike ReicheltPathology, Genentech, Inc., South San Francisco, California.
Ofer GuttmanCancer Immunology, Genentech, Inc., South San Francisco, California.
Thomas D WuBioinformatics, Genentech, Inc., South San Francisco, California.ORCID 0000-0003-4505-4531
Scot A MarstersCancer Immunology, Genentech, Inc., South San Francisco, California.
Anna ShemorryCancer Immunology, Genentech, Inc., South San Francisco, California.
David A LawrenceCancer Immunology, Genentech, Inc., South San Francisco, California.
David KanTranslational Oncology, Genentech, Inc., South San Francisco, California.
Ehud SegalTranslational Oncology, Genentech, Inc., South San Francisco, California.
Mark MerchantTranslational Oncology, Genentech, Inc., South San Francisco, California.
Klara TotpalTranslational Oncology, Genentech, Inc., South San Francisco, California.
Lisa M CrockerTranslational Oncology, Genentech, Inc., South San Francisco, California.
Kathryn MeshPathology, Genentech, Inc., South San Francisco, California.
Monika DohsePathology, Genentech, Inc., South San Francisco, California.
Margaret SolonPathology, Genentech, Inc., South San Francisco, California.
Zora ModrusanMolecular Biology, Genentech, Inc., South San Francisco, California.
Joachim RudolphDiscovery Chemistry, Genentech, Inc., South San Francisco, California.
Hartmut KoeppenPathology, Genentech, Inc., South San Francisco, California.
Peter WalterDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California.
Avi AshkenaziCancer Immunology, Genentech, Inc., South San Francisco, California. ashkenazi.avi@gene.com.
Genesys (United States) · USLpath (United States) · USHoward Hughes Medical Institute · USIntermolecular (United States) · USSunny BioDiscovery (United States) · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Cancer cells exploit the unfolded protein response (UPR) to mitigate endoplasmic reticulum (ER) stress caused by cellular oncogene activation and a hostile tumor microenvironment (TME). The key UPR sensor IRE1α resides in the ER and deploys a cytoplasmic kinase-endoribonuclease module to activate the transcription factor XBP1s, which facilitates ER-mediated protein folding. Studies of triple-negative breast cancer (TNBC)-a highly aggressive malignancy with a dismal posttreatment prognosis-implicate XBP1s in promoting tumor vascularization and progression. However, it remains unknown whether IRE1α adapts the ER in TNBC cells and modulates their TME, and whether IRE1α inhibition can enhance antiangiogenic therapy-previously found to be ineffective in patients with TNBC. To gauge IRE1α function, we defined an XBP1s-dependent gene signature, which revealed significant IRE1α pathway activation in multiple solid cancers, including TNBC. IRE1α knockout in TNBC cells markedly reversed substantial ultrastructural expansion of their ER upon growth

Indexed as

Angiogenesis InhibitorsAnimalsAntineoplastic Agents, ImmunologicalCell Line, TumorEndoplasmic Reticulum StressEndoribonucleasesFemaleGene Knockout TechniquesHumansMiceMice, SCIDNeovascularization, PathologicProtein Serine-Threonine KinasesRNA, MessengerTriple Negative Breast NeoplasmsTumor MicroenvironmentAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalEndoribonucleasesERN1 protein, humanProtein Serine-Threonine KinasesRNA, MessengerVascular Endothelial Growth Factor AVEGFA protein, humanX-Box Binding Protein 1XBP1 protein, human

Identifiers

PMID32265225
PMCPMC7272310
OpenAlexW3014954380

What OpenQuestion holds

Textmetadata
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.