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
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603
Caught up in a Wnt storm: Wnt signaling in cancer
Giles, R. H., van Es, J. H., & Clevers, H. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(03)00005-2 · Cited by 1,482 · cited 1×
“The Wnt/Wingless pathway plays a pivotal role in embryonic development and adult homeostasis by regulating cell fate, proliferation, and differentiation, and it is aberrantly reactivated in various human cancers ( 1 ).”
BackgroundMolecular pathogenesis of human hepatocellular carcinoma
Thorgeirsson, S. S., & Grisham, J. W. (2002) · Nature Genetics · doi:10.1038/ng0802-339 · Cited by 1,456
Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas
Coste, A. D. L., Romagnolo, B., Billuart, P., Renard, C.-A., Buendia, M., Soubrane, O., Fabrè, M., Chelly, J., Beldjord, C., Kahn, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8847 · Cited by 1,157
Self-citationLaurent‐Puig, P., Legoix, P., Bluteau, O., Belghiti, J., Franco, D., Binot, F., Monges, G. M., Thomas, G. D., Bioulac‐Sage, P., & Zucman‐Rossi, J. (2001) · Gastroenterology · doi:10.1053/gast.2001.24798 · Cited by 582 · cited 2×
“It suggests that the Wnt/h-catenin pathway was activated through other means, such as overexpression of Frizzled-7 or loss-of-function mutations of Axin ( 9 ).”
BackgroundApc Tumor Suppressor Gene Is the “Zonation-Keeper” of Mouse Liver
Benhamouche, S., Decaens, T., Godard, C., Chambrey, R., Rickman, D. S., Moinard, C., Vasseur-Cognet, M., Kuo, C. J., Kahn, A., Perret, C., et al. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.03.015 · Cited by 543
Self-citationMutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome
Bamshad, M., Lin, R. C., Law, D. J., Watkins, W. S., Krakowiak, P. A., Moore, M. E., Franceschini, P., Lala, R., Holmes, L. B., Gebuhr, T. C., et al. (1997) · Nature Genetics · doi:10.1038/ng0797-311 · Cited by 540 · cited 2×
“In particular, Tbx3 is expressed in the mesenchyme at the limb bud margins and in the mammary buds, correlating with defects in anteroposterior patterning and mammary gland induction in Tbx3-deficient mice and in UMS patients (22, 23 , 38).”
BackgroundT (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specificationPreprint
Yamaguchi, T. P., Takada, S., Yoshikawa, Y., Wu, N., & McMahon, A. P. (1999) · Genes & Development · doi:10.1101/gad.13.24.3185 · Cited by 527
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“We show that Tbx3 expression is activated by Wnt/h-catenin signaling in murine as well as in human liver tumors, confirming the value of mouse models to study molecular events that occur in HCC ( 34 ).”
BackgroundNew targets of β-catenin signaling in the liver are involved in the glutamine metabolism
Cadoret, A., Ovejero, C., Terris, B., Souil, E., Lévy, L., Lamers, W. H., Kitajewski, J., Kahn, A., & Perret, C. (2002) · Oncogene · doi:10.1038/sj.onc.1206118 · Cited by 412
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Cairo, S., Armengol, C., de Reyniès, A., Yu, W., Thomas, E., Renard, C.-A., Goga, A., Balakrishnan, A., Semeraro, M., Gresh, L., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.002 · Cited by 530
“We have shown recently that inhibition of b-catenin impairs anchorage-independent growth of hepatoma cells in vitro (Renard et al., 2007).”
BackgroundSelf-citationIdentification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis
Peters, U., Jiao, S., Schumacher, F. R., Hutter, C. M., Aragaki, A. K., Baron, J. A., Berndt, S. I., Bezieau, S., Brenner, H., Butterbach, K., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.12.020 · Cited by 324
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Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON), Ghoussaini, M., (FBCS), F. B. C. S., The Gene Environment Interaction of Breast Cancer in Germany (GENICA) Network, kConFab Investigators, Australian Ovarian Cancer Study Group, Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M. K., et al. (2012) · Nature Genetics · doi:10.1038/ng.1049 · Cited by 285
“and that TBX3 is a direct downstream target of the Wnt–β-catenin pathwa”
BackgroundKong, L., Pokatayev, V., Lefkovith, A. J., Carter, G. T., Creasey, E. A., Krishna, C., Subramanian, S., Kochar, B. D., Ashenberg, O., Lau, H., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.002 · Cited by 291
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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