Tbx3 Represses E-Cadherin Expression and Enhances Melanoma Invasiveness
Abstract
The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21CIP1 expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels. [Cancer Res 2008;68(19):7872–81]
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Ectopic expression of Tbx3 increases the invasiveness of melanoma cell lines.
“Ectopic expression of Tbx3 has suggested that this protein has the ability to increase the invasiveness of melanoma cell lines.43”
Tbx3 may induce melanoma cell invasion by binding the E-cadherin promoter to repress its transcription.
“Recent studies have also indicated that Tbx3 may induce melanoma cell invasion via binding the E-cadherin promoter to repress its transcription.43”
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“Furthermore, there is evidence that TBX2 and TBX3 are differentially expressed in some cancers which appears to relate, in part, to their ability to repress one another (Mohamad et al., 2018; Rodriguez et al., 2008).”
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- Authors
- Rodriguez, M., Aladowicz, E., Lanfrancone, L., & Goding, C. R.
- Affiliations
- 1Signalling and Development Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, United Kingdom;
- 3IFOM-IEO Campus, Milan, Italy
- IFOM (IT)
- University of Oxford (GB)
- Venue
- Cancer Research
- Published
- 2008-09-30
- Volume
- 68
- Issue
- 19
- Pages
- 7872-7881
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2131515143
- Cited by
- 157
- References
- 3
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 16 · 2013: 16 · 2012: 11
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- TBX3, TBX2, E-cadherin, melanoma, tumor invasion, transcriptional repression, p21, cellular senescence, tumor progression
- MeSH terms
- Base Sequence, Cell Adhesion, Humans, Melanoma, Neoplasm Invasiveness, Promoter Regions, Genetic, Protein Binding, Tumor Cells, Cultured, Down-Regulation, Cadherins, Gene Expression Regulation, Neoplastic, Cellular Senescence, Calcium Signaling, T-Box Domain Proteins, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21
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