The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Tbx3 Is a Downstream Target of the Wnt/β-Catenin Pathway and a Critical Mediator of β-Catenin Survival Functions in Liver Cancer
Published version of a preprint
Abstract
Tbx3 encodes a transcriptional repressor that is important for diverse patterning events during development, and Tbx3 mutation in humans causes the ulnar-mammary syndrome. Here, we describe the identification of Tbx3 in array-based search for genes downstream Wnt/β-catenin that are implicated in liver tumorigenesis. Overexpression of Tbx3 is closely associated with the mutational status of β-catenin in murine liver tumors induced by Myc as well as in human hepatocellular carcinomas and hepatoblastomas. Moreover, Tbx3 transcription is activated by ectopic expression of β-catenin in mouse liver and in human tumor cell lines. Evidence that Tbx3 transcription is directly regulated by β-catenin is provided by chromatin immunoprecipitation and reporter assays. Although HepG2 cells stably transfected with Tbx3 display moderately enhanced growth rate, the dominant negative mutant Tbx3-Y149S drastically inhibits hepatoma cell growth in vitro and in vivo. Moreover, small interfering RNAs (siRNA) directed against Tbx3 inhibit anchorage-independent growth of liver and colon carcinoma cells. We further show that inhibition of Tbx3 expression by specific siRNAs blocks β-catenin–mediated cell survival and renders cells sensitive to doxorubicin-induced apoptosis. Conversely, ectopic expression of Tbx3 inhibits apoptosis induced by β-catenin depletion. Marked overexpression of Tbx3 in a subset of hepatoblastomas is associated with chemotherapy-resistant phenotype and unfavorable patient outcome. These results reveal an unsuspected role of Tbx3 as a mediator of β-catenin activities on cell proliferation and survival and as an important player in liver tumorigenesis. [Cancer Res 2007;67(3):901–10]
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Cites
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“In liver cancer, Wnt/β-catenin signaling is upstream of TBX3 and a critical mediator of β-catenin functions (24).”
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“It has been reported to promote evasion of apoptosi s, migration, invasion and tumour forming ability (Brummelkamp et al., 2002; Ito et al., 2005; Renard et al., 2007; Peres et al., 2010).”
BackgroundMutations in exon 2 ofTBX3are rare in common human tumors
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“80 associated with β-catenin mutational status in HCC [170].”
BackgroundThe Role of T-box (Tbx) 2 in Osteoblast Function
Francis, N. (2011) · OpenCommons - UConn (University of Connecticut)
TBX3 Is Overexpressed in Breast Cancer and Represses p14ARF by Interacting with Histone Deacetylases
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“Recent exciting studies show that TBX3 is a downstream target of Wnt/ h-catenin in liver cancer, and that Wnt/h-catenin can up-regulate TBX3 expression ( 14 ).”
BackgroundTBX2 and TBX3: The special value for anticancer drug targets
Lu, J., Li, X.-P., Dong, Q., Kung, H.-F., & He, M.-L. (2010) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.07.001 · Cited by 57
“The abnormal expression of TBX2 and TBX3 has been reported in various cancers (Table 1) , including melanoma, breast, pancreatic, liver, lung, ovarian, bladder and cervical cancers [28, [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] .”
Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma
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“In addition to its key role in development, TBX3 expression has also been found to be amplified or over-expressed in many different cancer types including breast, cervix, ovary, pancreas, liver cancers and melanomas [9-14].”
BackgroundInfluentialUV-mediated Regulation of the Anti-senescence Factor Tbx2
Abrahams, A., Mowla, S., Parker, M. I., Goding, C. R., & Prince, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705651200 · Cited by 45
Human Breast Progenitor Cell Numbers Are Regulated by WNT and TBX3
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“increased by WNT signaling in various cancer cell lines [60,61].”
BackgroundThe transcriptional regulator TBX3 promotes progression from non-invasive to invasive breast cancer
Krstic, M., Macmillan, C. D., Leong, H. S., Clifford, A. G., Souter, L. H., Dales, D. W., Postenka, C. O., Chambers, A. F., & Tuck, A. B. (2016) · BMC Cancer · doi:10.1186/s12885-016-2697-z · Cited by 23
“TBX3 expression has also been found to be associated with cell survival in hepatocellular carcinoma, where it is induced by Wnt/β-catenin signalling [15].”
Miao, Z.-F., Liu, X.-Y., Xu, H.-M., Wang, Z.-N., Zhao, T.-T., Song, Y.-X., Xing, Y.-N., Huang, J.-Y., Zhang, J.-Y., Xu, H., et al. (2016) · Virchows Archiv · doi:10.1007/s00428-016-2007-9 · Cited by 20
“Tbx3 drives malignant progression of hepatocellular carcinoma by regulating Wnt/ β-catenin signaling [16].”
Background
Metadata
- Authors
- Renard, C.-A., Labalette, C., Armengol, C., Cougot, D., Wei, Y., Cairo, S., Pineau, P., Neuveut, C., de Reyniès, A., Dejean, A., Perret, C., & Buendia, M.-A.
- Affiliations
- 1Institut National de la Sante et de la Recherche Medicale, U579;
- Inserm (FR)
- 4Ligue Nationale contre le Cancer;
- ORCID
- Venue
- Cancer Research
- Published
- 2007-02-01
- Volume
- 67
- Issue
- 3
- Pages
- 901-910
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2142575284
- Cited by
- 157
- References
- 51
- Citations by year
- 2025: 3 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 12 · 2013: 14 · 2012: 12
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- HAL (Le Centre pour la Communication Scientifique Directe) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- TBX3, Wnt/β-catenin signaling, hepatocarcinogenesis, hepatocellular carcinoma, hepatoblastoma, transcriptional repression, doxorubicin sensitivity, apoptosis, chemoresistance, cell proliferation, ulnar-mammary syndrome
- MeSH terms
- Animals, Cell Adhesion, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Liver Neoplasms, Experimental, Mice, Transgenic, Mutation, Promoter Regions, Genetic, Transcription, Genetic, Transfection, Genes, myc, Apoptosis, T-Box Domain Proteins, RNA, Small Interfering, Cell Line, Tumor, Cell Growth Processes, Wnt Proteins, beta Catenin, Mice, TCF Transcription Factors
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