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TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
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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“At very low levels, TGF-β act as chemo-attractant for fibroblasts248,249.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [248]
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Metadata
- 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
- 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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