Cited by 1,401TGF-β signaling in diseasesLiver physiology and pathologyCancer Cells and Metastasis

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TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia

Bhowmick, Neil A., Chytil, Anna, Plieth, David, Gorska, Agnieszka E., Dumont, Nancy, Shappell, Scott, Washington, M. Kay, Neilson, Eric G., Moses, Harold L.·2004·Science

DOI 10.1126/science.1090922

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Abstract

Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor–β (TGF-β) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-β type II receptor gene in mouse fibroblasts ( Tgfbr2 fspKO ). The loss of TGF-β responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-β signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.

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Authors: Bhowmick, N. A., Chytil, A., Plieth, D., Gorska, A. E., Dumont, N., Shappell, S., Washington, M. K., Neilson, E. G., & Moses, H. L.
Affiliations: Vanderbilt University (US)
Corresponding author: Moses, Harold L.
ORCID: Bhowmick, Neil A.
Gorska, Agnieszka E.
Dumont, Nancy
Washington, M. Kay
Neilson, Eric G.
Moses, Harold L.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2004-02-06
Volume: 303
Issue: 5659
Pages: 848-851
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1090922
OpenAlex: W2031300004
Cited by: 1,401
References: 26
Citations by year: 2026: 19 · 2025: 23 · 2024: 26 · 2023: 43 · 2022: 42 · 2021: 42 · 2020: 47 · 2019: 36 · 2018: 52 · 2017: 57 · 2016: 50 · 2015: 73 · 2014: 78 · 2013: 92 · 2012: 94
FWCI: 33.34
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA085492, CA85492, CA102162, CA68485, R01CA102162, P30CA068485)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK046282, DK46282)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41943, P30AR041943)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: TGF-beta signaling, fibroblasts, epithelial-mesenchymal interactions, TGFBR2, conditional knockout, stromal cells, prostatic intraepithelial neoplasia, hepatocyte growth factor, paracrine signaling, epithelial cell proliferation, carcinogenesis
MeSH terms: Receptor, Transforming Growth Factor-beta Type II, Animals, Carcinoma, Squamous Cell, Cell Division, Cell Transformation, Neoplastic, Cells, Cultured, Epithelial Cells, Female, Fibroblasts, Gastric Mucosa, Male, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Glandular and Epithelial, Prostate, Recombination, Genetic, Stomach, Stomach Neoplasms, Signal Transduction, Transforming Growth Factor beta, Stromal Cells, Hepatocyte Growth Factor, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Mice, Knockout, Prostatic Intraepithelial Neoplasia, Proto-Oncogene Proteins c-met, Mice

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TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia

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