Evidence map›Paper›PMID 33568624›Full record

ArticleOncogenesis2021

TGF-β1-mediated transition of resident fibroblasts to cancer-associated fibroblasts promotes cancer metastasis in gastrointestinal stromal tumor.

Hyunho Yoon, Chih-Min Tang, Sudeep Banerjee, Antonio L Delgado, Mayra Yebra, Jacob Davis, Jason K Sicklick

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

Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
13.0field-weighted citation impact, top 1% 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

77 citing papers in PubMed, 113 citations in OpenAlex.

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  20. PDPNCell communication and signaling : CCS · 2025
    Article

17 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

7 authors at 3 institutions in 1 country.

Hyunho YoonDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Chih-Min TangDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Sudeep BanerjeeDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Antonio L DelgadoDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Mayra YebraDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Jacob DavisDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA.
Jason K SicklickDepartment of Surgery, Division of Surgical Oncology, University of California, San Diego, CA, USA. jsicklick@health.ucsd.edu.ORCID http://orcid.org/0000-0003-4403-0271
University of California San Diego · USUC San Diego Health System · USUniversity of California, Los Angeles · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
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
FDA HHS R01 FD006334NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA226803
6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are the most abundant cells in the tumor microenvironment. Crosstalk between tumor cells and CAFs contributes to tumor survival in most epithelial cancers. Recently, utilizing gastrointestinal stromal tumor (GIST) as a model for sarcomas, we identified paracrine networks by which CAFs promote tumor progression and metastasis. However, the mechanisms by which CAFs arise in sarcomas remain unclear. Here, RNA sequencing analysis revealed that transforming growth factor-β1 (TGF-β1) is highly expressed in both tumor cells and CAFs. To determine the functional role of TGF-β1, we treated normal gastric fibroblasts (GFs) with recombinant TGF-β1, which caused the GFs to adopt a more stellate morphology, as well as increased the mRNA expression of CAF-mediated genes (CCL2, RAB3B, and TNC) and genes encoding fibroblast growth factors (FGFs). Moreover, while either GIST or CAF conditioned media enhanced the transition from GFs to CAFs, a TGF-β1-blocking antibody attenuated this effect. Transwell migration assays revealed that the TGF-β1-mediated transition from GFs to CAFs enhanced tumor cell migration. This migratory effect was abrogated by an anti-TGF-β1 antibody, suggesting that TGF-β1 secreted from GIST cells or CAFs is associated with GIST migration via GF-to-CAF transition. In addition, the murine spleen-to-liver metastasis model showed that GF pre-treated with TGF-β1 promoted GIST metastasis. Collectively, these findings reveal unappreciated crosstalk among tumor cells, CAFs, and normal resident fibroblasts in the stroma of sarcomas, which enhances a GF-to-CAF transition associated with tumor migration and metastasis.

Identifiers

PMID33568624
PMCPMC7876107
OpenAlexW3126758049

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.