The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
Open accessAbstract
The T-box transcription factor, TBX3, plays an important role in embryonic development, and haploinsufficiency of TBX3 causes ulnar–mammary syndrome. Overexpression of TBX3, on the other hand, is associated with several cancers, and preliminary evidence suggests that increased levels of TBX3 may inhibit cell proliferation but promote tumor migration and invasion. Although this suggests that deregulated levels of TBX3 are deleterious in development and promotes disease, very little is known about the signaling pathways that regulate TBX3 expression. Here we show that overexpressing TBX3 inhibits proliferative ability while promoting the migration of breast epithelial cells. We demonstrate that the transforming growth factor β1 (TGF-β1) pathway up-regulates TBX3 protein and mRNA levels and show a detailed transcriptional mechanism by which this occurs. Using in vitro and in vivo assays, we show that Smad3/4 and JunB bind and cooperatively regulate TBX3 promoter activity through a Smad-binding element at −67 base pairs. Further, we show that TBX3 plays a pivotal role in mediating the antiproliferative and promigratory role of TGF-β1 in breast epithelial and skin keratinocytes. This study identifies the TGF-β1 signaling pathway as a potentially important player in the regulation of TBX3 in development and cancer.
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Although TBX3 promotes migration and invasiveness of cancer cells, it negatively regulates cell proliferation.
“More recently, it was recognized that although TBX3 promotes migration and invasiveness of cancer cells, it negatively regulates cell proliferation [37, 63].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [37]
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- Authors
- Li, J., Weinberg, M. S., Zerbini, L., & Prince, S.
- Affiliations
- University of Cape Town (ZA)
- University of the Witwatersrand (ZA)
- Corresponding author
- Prince, Sharon
- Venue
- Molecular Biology of the Cell
- Published
- 2013-11-15
- Volume
- 24
- Issue
- 22
- Pages
- 3569-3576
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC3826994
- OpenAlex
- W2109174791
- Cited by
- 56
- References
- 33
- Citations by year
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- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- South African Medical Research Council
- Cancer Association of South Africa
- University of Cape Town
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- TBX3, TGF-β1 signaling, Smad3/4, JunB, transcriptional regulation, breast epithelial cells, keratinocytes, cell migration, cell proliferation, oncogenic transcription factor, Smad binding element, ulnar-mammary syndrome, tumor invasion
- MeSH terms
- Binding Sites, Cell Line, Cell Movement, Cell Transformation, Neoplastic, Epithelial Cells, Female, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Skin, Transcription Factors, Transcription, Genetic, Signal Transduction, Keratinocytes, T-Box Domain Proteins, Mammary Glands, Human, Cell Proliferation, Smad3 Protein, Smad4 Protein, Transforming Growth Factor beta1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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