Evidence map›Paper›PMID 29738634›Full record

ArticleMolecular oncology2018

GRP78-mediated antioxidant response and ABC transporter activity confers chemoresistance to pancreatic cancer cells.

Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee

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

Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 15% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

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  12. Ferroptosis: An Emerging Target for Bladder Cancer Therapy.Current issues in molecular biology · 2023
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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

7 authors at 3 institutions in 1 country.

Patricia DauerDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Nikita S SharmaDepartment of Surgery, University of Miami, FL, USA.
Vineet K GuptaDepartment of Surgery, University of Miami, FL, USA.
Alice NomuraDepartment of Surgery, University of Miami, FL, USA.
Vikas DudejaDepartment of Surgery, University of Miami, FL, USA.
Ashok SalujaDepartment of Surgery, University of Miami, FL, USA.
Sulagna BanerjeeDepartment of Surgery, University of Miami, FL, USA.
Sylvester Comprehensive Cancer Center · USUniversity of Miami · USUniversity of Minnesota · US

Funding

The Inhibition of HSP70 Induces Apoptosis in Pancreatic Cancer CellsR01CA124723 · NCI · UNIVERSITY OF MINNESOTA · PI GILBOA, ELI, RAMAKRISHNAN, SUNDARAM · 2007 to 2022
$4.5M
Triptolide Augments Death Receptor Mediated Apoptosis in Pancreatic CancerR01CA170946 · NCI · UNIVERSITY OF MINNESOTA · PI SALUJA, ASHOK K · 2012 to 2016
$2.4M
Functional Significance of CD133 in Pancreatic CancerR01CA184274 · NCI · UNIVERSITY OF MINNESOTA · PI BANERJEE, SULAGNA · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA124723NCI NIH HHS R01 CA170946NCI NIH HHS R01 CA184274
6 · The paper itself

Abstract

Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded protein response (UPR) is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In this study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS). We also show that these effects can be mediated by the activity of specificity protein 1 (SP1), a transcription factor overexpressed in pancreatic cancer. Thus, inhibition of SP1 negatively affects the UPR, deregulates the antioxidant response of NRF2, as well as ABC transporter activity by inhibiting GRP78-mediated ER homeostasis. Sp1 and NRF2 have been classified as nononcogene addiction genes and thus are imperative to understanding the molecular mechanism of resistance. These finding have huge clinical relevance as both Sp1 and GRP78 are overexpressed in pancreatic cancer patients and increased expression of these proteins is indicative of poor prognosis. Understanding how these proteins may regulate chemoresistance phenotype of this aggressive cancer may pave the way for development of efficacious therapy for this devastating disease.

Indexed as

Drug Resistance, NeoplasmAnimalsAntibiotics, AntineoplasticATP-Binding Cassette TransportersCell DeathCell Line, TumorDisease ProgressionEndoplasmic ReticulumEndoplasmic Reticulum Chaperone BiPGene ExpressionGene SilencingHeat-Shock ProteinsHomeostasisHumansMiceMice, NudeAntibiotics, AntineoplasticATP-Binding Cassette TransportersEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mouseNFE2L2 protein, humanNF-E2-Related Factor 2PlicamycinReactive Oxygen SpeciesSp1 Transcription FactorchemoresistanceGRP78Sp1unfolded protein response

Identifiers

PMID29738634
PMCPMC6120253
OpenAlexW2803073176

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.