Evidence map›Paper›PMID 33603171›Full record

ArticleOncogene2021

Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis.

Hyunho Yoon, Chih-Min Tang, Sudeep Banerjee, Mayra Yebra, Sangkyu Noh, Adam M Burgoyne, Jorge De la Torre, Martina De Siena, Mengyuan Liu, Lillian R Klug and 12 more

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

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 49 citations in OpenAlex.

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  18. Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

22 authors at 7 institutions in 3 countries.

Hyunho YoonDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Chih-Min TangDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Sudeep BanerjeeDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Mayra YebraDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Sangkyu NohDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Adam M BurgoyneDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Jorge De la TorreDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Martina De SienaDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.ORCID http://orcid.org/0000-0003-4913-7254
Mengyuan LiuDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Lillian R KlugDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA.
Yoon Young ChoiDivision of Biomedical Informatics, Moores Cancer Center, University of California, San Diego, CA, USA.
Mojgan HosseiniDepartment of Pathology, Moores Cancer Center, University of California, San Diego, CA, USA.
Antonio L DelgadoDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Zhiyong WangDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, CA, USA.
Randall P FrenchDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Andrew LowyDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA.
Ronald P DeMatteoDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Michael C HeinrichPortland VA Health Care System, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0003-3790-0478
Alfredo A MolinoloDepartment of Pathology, Moores Cancer Center, University of California, San Diego, CA, USA.
J Silvio GutkindDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, CA, USA.
Olivier HarismendyDivision of Biomedical Informatics, Moores Cancer Center, University of California, San Diego, CA, USA.
Jason K SicklickDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA, USA. jsicklick@health.ucsd.edu.ORCID http://orcid.org/0000-0003-4403-0271
University of California San Diego · USOregon Health & Science University · USUniversity of Pennsylvania · USAgostino Gemelli University Polyclinic · ITUC San Diego Health System · USUniversity of California, Los Angeles · USYonsei University · KR

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
Targeting Drug-Resistant Cancer Stem Cell Niches of Gastrointestinal Stromal TumorR01CA226803 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2019 to 2023
$2.1M
Investigation of DNA Damaging Agents in GIST with Metabolic DysfunctionR01FD006334 · FDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2019 to 2021
$1.5M
Novel models for functional profiling of germline SDH variants associated with cancerR21CA263400 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI HEINRICH, MICHAEL C · 2021 to 2022
$320k
Regulation of oncogenic KIT by LMTK3I01BX000338 · VA · PORTLAND VA MEDICAL CENTER · PI HEINRICH, MICHAEL C · 2009 to 2019
–
BLRD VA I01 BX000338BLRD VA I01 BX005358FDA HHS R01 FD006334NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA226803NCI NIH HHS R21 CA263400
6 · The paper itself

Abstract

Targeted therapies for gastrointestinal stromal tumor (GIST) are modestly effective, but GIST cannot be cured with single agent tyrosine kinase inhibitors. In this study, we sought to identify new therapeutic targets in GIST by investigating the tumor microenvironment. Here, we identified a paracrine signaling network by which cancer-associated fibroblasts (CAFs) drive GIST growth and metastasis. Specifically, CAFs isolated from human tumors were found to produce high levels of platelet-derived growth factor C (PDGFC), which activated PDGFC-PDGFRA signal transduction in GIST cells that regulated the expression of SLUG, an epithelial-mesenchymal transition (EMT) transcription factor and downstream target of PDGFRA signaling. Together, this paracrine induce signal transduction cascade promoted tumor growth and metastasis in vivo. Moreover, in metastatic GIST patients, SLUG expression positively correlated with tumor size and mitotic index. Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Taken together, we identified a previously unappreciated cellular target for GIST therapy in order to improve disease control and cure rates.

Indexed as

Cancer-Associated FibroblastsCell Line, TumorEpithelial-Mesenchymal TransitionGastrointestinal Stromal TumorsHumansLymphokinesNeoplasm MetastasisParacrine CommunicationPhosphatidylinositol 3-KinasesPlatelet-Derived Growth FactorProtein Kinase InhibitorsReceptor, Platelet-Derived Growth Factor alphaSignal TransductionSnail Family Transcription FactorsTOR Serine-Threonine KinasesTumor MicroenvironmentLymphokinesPhosphatidylinositol 3-KinasesPlatelet-Derived Growth Factorplatelet-derived growth factor CProtein Kinase InhibitorsReceptor, Platelet-Derived Growth Factor alphaSNAI1 protein, humanSnail Family Transcription FactorsTOR Serine-Threonine Kinases

Identifiers

PMID33603171
PMCPMC7979540
OpenAlexW3129226110

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.