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

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. +1 more·2004·Science

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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Crossref · 10.1126/science.1090922

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24 of 24 references verified0 citation errors · 0 not checkable

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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.
Venue
Science
Published
2004-02-06
Volume
303
Issue
5659
Pages
848-851
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
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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