ArticleCell2019
A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04927611 (Single-cell Sequencing and Establishment of Cell Lines, Organoids, and Transplanted Tumor Models in Neuroendocrine Neoplasm), which is not on this map. Cited by 93 papers.
0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
8.6field-weighted citation impact, top 2% of its field
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.
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.
Single-cell Sequencing and Establishment of Cell Lines, Organoids, and Transplanted Tumor Models in Neuroendocrine Neoplasm
Who cites it
93 citing papers in PubMed, 167 citations in OpenAlex.
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- Regulation of lung cancer initiation and progression by the stem cell determinant Musashi.eLife · 2025Article
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- Stearoyl CoA desaturase inhibition can effectively induce apoptosis in bladder cancer stem cells.Cancer cell international · 2024Article
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33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
33 authors at 9 institutions in 3 countries.
Nikki K LytleDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
L Paige FergusonDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Nirakar RajbhandariDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Kathryn GilroyInstitute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1BD, UK.
Raymond G FoxDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Anagha DeshpandeTumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Christian M SchürchBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA, USA.
Michael HamiltonDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Neil RobertsonInstitute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1BD, UK.
Wei LinMolecular Medicine Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
Pawan NoelMolecular Medicine Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
Martin WartenbergInstitute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland.
Inti ZlobecInstitute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland.
Micha EichmannInstitute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland.
José A GalvánInstitute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland.
Eva KaramitopoulouInstitute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland.
Tami GildermanDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Lourdes Adriana EsparzaDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Yutaka ShimaDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Philipp SpahnDepartment of Pediatrics and the Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Randall FrenchMoores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Nathan E LewisDepartment of Pediatrics and the Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Kathleen M FischCenter for Computational Biology and Bioinformatics, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Roman SasikCenter for Computational Biology and Bioinformatics, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Sara Brin RosenthalCenter for Computational Biology and Bioinformatics, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Marcie KritzikDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Daniel Von HoffMolecular Medicine Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
Haiyong HanMolecular Medicine Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
Trey IdekerMoores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Aniruddha J DeshpandeTumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Andrew M LowyMoores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA; Division of Surgical Oncology, Department of Surgery, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Peter D AdamsInstitute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1BD, UK; Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Tannishtha ReyaDepartment of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA. Electronic address: treya@ucsd.edu.
University of California, San Diego · USSanford Consortium for Regenerative Medicine · USUniversity of Bern · CHTranslational Genomics Research Institute · USUniversity of Glasgow · GBSanford Burnham Prebys Medical Discovery Institute · USFoundation Center · USNovo Nordisk (United States) · USStanford University · US
Funding
UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3MGRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5MMolecular strategies for early detection and targeting of cancerR35CA197699 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Tannishtha Reya · 2015 to 2026
$11.2MBlood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4MUnraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3MRON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9MMusashi-mediated control of pancreatic cancer growth and progressionR01CA186043 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M, REYA, TANNISHTHA · 2015 to 2019
$2.1MTargeting Stromal Collagen in Pancreatic CancerR01CA169281 · NCI · TRANSLATIONAL GENOMICS RESEARCH INST · PI HAN, HAIYONG, VON HOFF, DANIEL D · 2013 to 2017
$1.9MStem cell signals in pancreatic adenocarcinoma metastasis and therapy resistanceF31CA206416 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LYTLE, NIKKI KATHERINE · 2016 to 2017
$75kCancer Research UK C10652-A16566NCATS NIH HHS UL1 TR001442NCI NIH HHS F31 CA206416NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA169281NCI NIH HHS R01 CA186043NCI NIH HHS R35 CA197699NHLBI NIH HHS T32 HL086344NIGMS NIH HHS R35 GM119850NIGMS NIH HHS T32 GM007752
Abstract
Drug resistance and relapse remain key challenges in pancreatic cancer. Here, we have used RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drive tumorigenesis and progression. This integrated genomic approach revealed an unexpected utilization of immuno-regulatory signals by pancreatic cancer epithelial cells. In particular, the nuclear hormone receptor retinoic-acid-receptor-related orphan receptor gamma (RORγ), known to drive inflammation and T cell differentiation, was upregulated during pancreatic cancer progression, and its genetic or pharmacologic inhibition led to a striking defect in pancreatic cancer growth and a marked improvement in survival. Further, a large-scale retrospective analysis in patients revealed that RORγ expression may predict pancreatic cancer aggressiveness, as it positively correlated with advanced disease and metastasis. Collectively, these data identify an orthogonal co-option of immuno-regulatory signals by pancreatic cancer stem cells, suggesting that autoimmune drugs should be evaluated as novel treatment strategies for pancreatic cancer patients.
Indexed as
AdenocarcinomaAnimalsCell Adhesion MoleculesCell DifferentiationEpigenesis, GeneticGene LibraryHumansMiceMice, KnockoutMice, SCIDNeoplastic Stem CellsNuclear Receptor Subfamily 1, Group F, Member 3Pancreatic NeoplasmsReceptors, G-Protein-CoupledReceptors, Interleukin-10RNA InterferenceCell Adhesion MoleculesNuclear Receptor Subfamily 1, Group F, Member 3Receptors, G-Protein-CoupledReceptors, Interleukin-10RNA, Small Interferingcancercancer stem cellscytokinesimmuneMsiMusashipancreatic cancerPDACRORgstem cells
Identifiers
What Socratic holds
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Read underepoch 390
Registered trials
NCT04927611ClinicalTrials.gov
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 Socratic graph.