Evidence map›Paper›PMID 29092903›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018

GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

Shu Z Wiley, Krishna Sriram, Wenjing Liang, Sarah E Chang, Randall French, Thalia McCann, Jason Sicklick, Hiroshi Nishihara, Andrew M Lowy, Paul A Insel

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

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. 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
4.0field-weighted citation impact, top 5% 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, 110 citations in OpenAlex.

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  19. Role of pH-sensing receptors in colitis.Pflugers Archiv : European journal of physiology · 2024
    Review
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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

10 authors at 3 institutions in 3 countries.

Shu Z WileyDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Krishna SriramDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Wenjing LiangDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Sarah E ChangDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Randall FrenchMoores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Thalia McCannDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Jason SicklickMoores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Hiroshi NishiharaDivision of Clinical Cancer Genomics, Hokkaido Cancer Center, Shiroishi-ku, Sapporo, Japan.
Andrew M LowyMoores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Paul A InselDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
University of California, San Diego · USJapan Cancer Society · JPQilu Hospital of Shandong University · CN

Funding

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
RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
Novel Allosteric Kinase Inhibitors Target Imatinib-Resistant GISTK08CA168999 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2014 to 2018
$888k
GPCRs: novel targets in cancer-associated fibroblastsR21CA189477 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI INSEL, PAUL A, LOWY, ANDREW M · 2014 to 2015
$371k
NCI NIH HHS K08 CA168999NCI NIH HHS R01 CA155620NCI NIH HHS R21 CA189477NCI NIH HHS T32 CA121938
6 · The paper itself

Abstract

The microenvironment of pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) generated by pancreatic cancer-associated fibroblasts (CAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). Using an unbiased GPCRomic array approach, we identified 82 G-protein-coupled receptors (GPCRs) commonly expressed by CAFs derived from 5 primary PDAC tumors. Compared with PSCs and PFs, CAFs have increased expression of GPR68 (a proton-sensing GPCR), with the results confirmed by immunoblotting, The Cancer Genome Atlas data, and immunohistochemistry of PDAC tumors. Co-culture of PSCs with PDAC cells, or incubation with TNF-α, induced GPR68 expression. GPR68 activation (by decreasing the extracellular pH) enhanced IL-6 expression via a cAMP/PKA/cAMP response element binding protein signaling pathway. Knockdown of GPR68 by short interfering RNA diminished low pH-induced production of IL-6 and enhancement of PDAC cell proliferation by CAF conditioned media. CAFs from other gastrointestinal cancers also express GPR68. PDAC cells thus induce expression by CAFs of GPR68, which senses the acidic microenvironment, thereby increasing production of fibrotic markers and IL-6 and promoting PDAC cell proliferation. CAF-expressed GPR68 is a mediator of low-pH-promoted regulation of the tumor microenvironments, in particular to PDAC cell-CAF interaction and may be a novel therapeutic target for pancreatic and perhaps other types of cancers.-Wiley, S. Z., Sriram, K., Liang, W., Chang, S. E., French, R., McCann, T., Sicklick, J., Nishihara, H., Lowy, A. M., Insel, P. A. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

Indexed as

Cell CommunicationTumor MicroenvironmentCancer-Associated FibroblastsCarcinoma, Pancreatic DuctalCell ProliferationCells, CulturedCoculture TechniquesCulture Media, ConditionedGene Expression Regulation, NeoplasticHumansPancreatic NeoplasmsPancreatic Stellate CellsReceptors, G-Protein-CoupledCulture Media, ConditionedGPR68 protein, humanReceptors, G-Protein-Coupledcyclic AMPGPCR signaling pathwaypancreatic cancertumor microenvironment

Identifiers

PMID29092903
PMCPMC5892729
OpenAlexW2767115634

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.