The T-box transcription factor 3 is a promising biomarker and a key regulator of the oncogenic phenotype of a diverse range of sarcoma subtypes
Open accessAbstract
Sarcomas represent a complex group of malignant neoplasms of mesenchymal origin and their heterogeneity poses a serious diagnostic and therapeutic challenge. There is therefore a need to elucidate the molecular mechanisms underpinning the pathogenesis of the more than 70 distinguishable sarcoma subtypes. The transcription factor TBX3, a critical developmental regulator, is overexpressed in several cancers of epithelial origin where it contributes to tumorigenesis by different molecular mechanisms. However, the status and role of TBX3 in sarcomas have not been reported. Here we show that a diverse subset of soft tissue and bone sarcoma cell lines and patient-derived sarcoma tissues express high levels of TBX3. We further explore the significance of this overexpression using a small interferring RNA approach and demonstrate that TBX3 promotes the migratory ability of chondrosarcoma, rhabdomyosarcoma and liposarcoma cells but inhibits fibrosarcoma cell migration. This suggested that TBX3 may play a key role in the development of different sarcoma subtypes by functioning as either an oncoprotein or as a brake to prevent tumour progression. To further explore this, TBX3 knockdown and overexpression cell culture models were established using chondrosarcoma and fibrosarcoma cells as representatives of each scenario, and the resulting cells were characterized with regard to key features of tumorigenesis. Results from in vitro and in vivo assays reveal that, while TBX3 promotes substrate-dependent and -independent cell proliferation, migration and tumour formation in chondrosarcoma cells, it discourages fibrosarcoma formation. Our findings provide novel evidence linking TBX3 to cancers of mesenchymal origin. Furthermore, we show that TBX3 may be a biomarker for the diagnosis of histologically dynamic sarcoma subtypes and that it impacts directly on their oncogenic phenotype. Indeed, we reveal that TBX3 may exhibit oncogene or tumour suppressor activity in sarcomas, which suggests that its role in cancer progression may rely on cellular context.
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Tissue-specific regulation of Tbx3 has been previously documented in mice and humans.
“This can be explained by tissue-specific regulation of Tbx3 that has been previously documented in mice [18] and humans [18, 25].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [25]
The Results and Discussion (page unavailable) show that TBX3 has different effects across human sarcoma cell types, with opposite effects on tumour growth in mouse xenografts. They do not document tissue-specific regulation of Tbx3 expression in mice and humans generally; the mouse experiments test implanted tumour cells. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe importance of TBX3 in relation to proliferation is underpinned by studies of its role in oncogenesis.
“The importance of TBX3 in relation to proliferation is underpinned by studies of its role in oncogenesis [24, 25, 58, 59].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [25]
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- Authors
- Willmer, T., Cooper, A., Sims, D., Govender, D., & Prince, S.
- Affiliations
- University of Cape Town (ZA)
- Corresponding author
- Cooper, A
- Prince, S
- Venue
- Oncogenesis
- Published
- 2016-02-22
- Volume
- 5
- Issue
- 2
- Pages
- e199-e199
- ISSN
- 2157-9024 (ISSN-L)
- PMC
- PMC5154352
- OpenAlex
- W2279817758
- Cited by
- 21
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 5 · 2017: 1 · 2016: 2
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Oncogenesis (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Cancer Association of South Africa
- University of Cape Town
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- TBX3, sarcoma, chondrosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, cell migration, cell proliferation, oncogenes, tumour suppressor, biomarkers, soft tissue sarcoma, bone sarcoma, mesenchymal tumors, carcinogenesis
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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