Evidence map›Paper›PMID 36646789›Full record

ArticleNature cell biology2023

Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation.

Chengsheng Wu, Taha Rakhshandehroo, Hiromi I Wettersten, Alejandro Campos, Tami von Schalscha, Shashi Jain, Ziqi Yu, Jiali Tan, Evangeline Mose, Betzaira G Childers and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.3field-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

28 citing papers in PubMed, 28 citations in OpenAlex.

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  14. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Chengsheng WuDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Taha RakhshandehrooDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Hiromi I WetterstenDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0001-7144-3122
Alejandro CamposDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Tami von SchalschaDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Shashi JainDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Ziqi YuDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-4952-8899
Jiali TanDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-7010-5268
Evangeline MoseDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Betzaira G ChildersDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Andrew M LowyDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Sara M WeisDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
David A ChereshDepartment of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA. dcheresh@health.ucsd.edu.
University of California San Diego · US

Funding

Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
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
Attacking stress tolerance in cancerR35CA220512 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 2018 to 2024
$6.5M
Blood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4M
RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
UCSD Research Training Program for VeterinariansT32OD017863 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ERNST, PETER B., SIGURDSON, CHRISTINA · 2014 to 2023
$2.0M
αvβ3-induced epithelial cancer progression via macrophage recruitmentK01OD030513 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WETTERSTEN, HIROMI INOUE · 2021 to 2025
$647k
NCI NIH HHS R01 CA045726NCI NIH HHS R01 CA155620NCI NIH HHS R35 CA220512NCI NIH HHS T32 CA009523NCI NIH HHS T32 CA121938NHLBI NIH HHS T32 HL086344NIH HHS K01 OD030513NIH HHS T32 OD017863
6 · The paper itself

Abstract

Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, drug resistance, self-renewal and tumour initiation. Pancreatic cancer cells gain LPAR4 expression in response to stress by downregulating a tumour suppressor, miR-139-5p. Even in the absence of exogenous lysophosphatidic acid, LPAR4-expressing tumour cells display an enrichment of extracellular matrix genes that are established drivers of cancer stemness. Mechanistically, upregulation of fibronectin via an LPAR4/AKT/CREB axis is indispensable for LPAR4-induced tumour initiation and stress tolerance. Moreover, ligation of this fibronectin-containing matrix via integrins α5β1 or αVβ3 can transfer stress tolerance to LPAR4-negative cells. Therefore, stress- or drug-induced LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix, allowing cells to survive 'isolation stress' and compensate for the absence of stromal-derived factors by creating their own tumour-initiating niche.

Indexed as

MicroRNAsPancreatic NeoplasmsReceptors, Purinergic P2Cell Transformation, NeoplasticExtracellular MatrixFibronectinsHumansReceptors, Lysophosphatidic AcidFibronectinsLPAR4 protein, humanMicroRNAsMIRN139 microRNA, humanReceptors, Lysophosphatidic AcidReceptors, Purinergic P2

Identifiers

PMID36646789
PMCPMC10280815
OpenAlexW4316507580

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.