Evidence map›Paper›PMID 28588081›Full record

ArticleScience signaling2017

Intercellular transmission of the unfolded protein response promotes survival and drug resistance in cancer cells.

Jeffrey J Rodvold, Kevin T Chiu, Nobuhiko Hiramatsu, Julia K Nussbacher, Valentina Galimberti, Navin R Mahadevan, Karl Willert, Jonathan H Lin, Maurizio Zanetti

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

Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Unfolded protein response and angiogenesis in malignancies.Biochimica et biophysica acta. Reviews on cancer · 2023
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

11 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

9 authors at 1 institution in 1 country.

Jeffrey J RodvoldLaboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA.ORCID http://orcid.org/0000-0002-4873-210X
Kevin T ChiuLaboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA.ORCID http://orcid.org/0000-0002-9087-8153
Nobuhiko HiramatsuDepartment of Pathology, University of California at San Diego, La Jolla, CA 92093, USA.
Julia K NussbacherDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.ORCID http://orcid.org/0000-0002-0626-4678
Valentina GalimbertiLaboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA.ORCID http://orcid.org/0000-0002-0506-8683
Navin R MahadevanLaboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA.
Karl WillertDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Jonathan H LinDepartment of Pathology, University of California at San Diego, La Jolla, CA 92093, USA.
Maurizio ZanettiLaboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA. mzanetti@ucsd.edu.ORCID http://orcid.org/0000-0001-6346-8776
University of California San Diego · US

Funding

Vision BiostatisticsP30EY022589 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Dirk-Uwe G Bartsch · 2012 to 2026
$10.3M
The Jackson Laboratory Center for Precision Genetics: From New Models to Novel TherapeuticsU54OD020351 · OD · JACKSON LABORATORY · PI BLAKE, JUDITH A · 2015 to 2019
$10.2M
Protein Homeostasis and Proteotoxicity MechanismsR01NS088485 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LIN, JONATHAN · 2015 to 2024
$3.0M
Cellular and Molecular Mechanisms of Age-Related Retinal DegenerationI01BX002284 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI LIN, JONATHAN · 2014 to 2023
–
BLRD VA I01 BX002284NEI NIH HHS P30 EY022589NIH HHS U54 OD020351NINDS NIH HHS R01 NS088485
6 · The paper itself

Abstract

Increased protein translation in cells and various factors in the tumor microenvironment can induce endoplasmic reticulum (ER) stress, which initiates the unfolded protein response (UPR). We have previously reported that factors released from cancer cells mounting a UPR induce a de novo UPR in bone marrow-derived myeloid cells, macrophages, and dendritic cells that facilitates protumorigenic characteristics in culture and tumor growth in vivo. We investigated whether this intercellular signaling, which we have termed transmissible ER stress (TERS), also operates between cancer cells and what its functional consequences were within the tumor. We found that TERS signaling induced a UPR in recipient human prostate cancer cells that included the cell surface expression of the chaperone GRP78. TERS also activated Wnt signaling in recipient cancer cells and enhanced resistance to nutrient starvation and common chemotherapies such as the proteasome inhibitor bortezomib and the microtubule inhibitor paclitaxel. TERS-induced activation of Wnt signaling required the UPR kinase and endonuclease IRE1. However, TERS-induced enhancement of cell survival was predominantly mediated by the UPR kinase PERK and a reduction in the abundance of the transcription factor ATF4, which prevented the activation of the transcription factor CHOP and, consequently, the induction of apoptosis. When implanted in mice, TERS-primed cancer cells gave rise to faster growing tumors than did vehicle-primed cancer cells. Collectively, our data demonstrate that TERS is a mechanism of intercellular communication through which tumor cells can adapt to stressful environments.

Indexed as

Drug ResistanceActivating Transcription Factor 4AnimalsAntineoplastic AgentsBortezomibCell SurvivaleIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressHeat-Shock ProteinsHumansMaleMiceMice, Inbred C57BLPaclitaxelProstatic NeoplasmsActivating Transcription Factor 4Antineoplastic AgentsBortezomibeIF-2 KinaseEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mousePaclitaxelTranscription Factor CHOPTubulin ModulatorsWnt Proteins

Identifiers

PMID28588081
PMCPMC5962022
OpenAlexW2624386673

What OpenQuestion holds

Textmetadata
LicenceTDM
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.