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]
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
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
Lee, J.-S., Chu, I.-S., Mikaelyan, A., Calvisi, D., Heo, J., Reddy, J., & Thorgeirsson, S. (2004) · Nature Genetics · doi:10.1038/ng1481 · Cited by 472 · cited 1×
“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
Self-citation
Cited by
Sorted by citations
Focal Gains of VEGFA and Molecular Classification of Hepatocellular Carcinoma
Chiang, D. Y., Villanueva, A., Hoshida, Y., Peix, J., Newell, P., Minguez, B., LeBlanc, A. C., Donovan, D. J., Thung, S. N., Solé, M., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0742 · Cited by 719
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
Genome-wide association analysis identifies three new breast cancer susceptibility loci
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
The Regulation of Testicular Descent and the Effects of Cryptorchidism
Hutson, J. M., Southwell, B. R., Li, R., Lie, G., Ismail, K. A., Harisis, G., & Chen, N. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1089 · Cited by 199
Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer
Cairo, S., Wang, Y., de Reyniès, A., Duroure, K., Dahan, J., Redon, M.-J., Fabrè, M., McClelland, M., Wang, X. W., Croce, C. M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009009107 · Cited by 196
Self-citationKim, M., Lee, H. C., Tsedensodnom, O., Hartley, R., Lim, Y., Yu, E., Merle, P., & Wands, J. R. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2007.12.020 · Cited by 185
“recently identified β-catenin target genes overexpressed in human HCC: GS [25], GPR49 [26], and Tbx3 [27].”
BackgroundAmini, S., Fathi, F., Mobalegi, J., Sofimajidpour, H., & Ghadimi, T. (2014) · Anatomy & Cell Biology · doi:10.5115/acb.2014.47.1.1 · Cited by 155
Cioffi, M., Trabulo, S. M. D., Sanchez-Ripoll, Y., Miranda‐Lorenzo, I., Lonardo, E., Dorado, J., Vieira, C. R., Ramírez, J. C., Hidalgo, M. M., Aicher, A., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-308470 · Cited by 138
Suzuki, A., Sekiya, S., Büscher, D., Izpisúa Belmonte, J. C., & Taniguchi, H. (2008) · Development · doi:10.1242/dev.016634 · Cited by 136
“Analogous to the results shown above, evidence from loss-of-function experiments demonstrated that Tbx3, which was also highly expressed in hepatic carcinoma cells, controlled a hyperproliferative feature of these cells (Renard et al., 2007).”
ResultWnt signaling and hepatocarcinogenesis: The hepatoblastoma model
Armengol, C., Cairo, S., Fabrè, M., & Buendia, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.07.012 · Cited by 137
Self-citationSixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma
Kim, S. M., Leem, S.-H., Chu, I., Park, Y.-Y., Kim, S. C., Kim, S. B., Park, E. S., Lim, J. Y., Heo, J., Kim, Y. J., et al. (2011) · Hepatology · doi:10.1002/hep.24813 · Cited by 132
The T‐box transcription factor Tbx2: Its role in development and possible implication in cancer
Abrahams, A., Parker, M. I., & Prince, S. (2009) · IUBMB Life · doi:10.1002/iub.275 · Cited by 123
“For example, Tbx2 and the very closely related factor Tbx3, have been implicated in cell cycle regulation and their expression is upregulated in a number of cancers, including breast (87, 88), pancreatic (89, 90), melanoma (91, 92), liver (93), and bladder (94).”
BackgroundHu, S., Liu, S., Bian, Y., Poddar, M., Singh, S., Cao, C., McGaughey, J., Bell, A., Blazer, L. L., Adams, J. J., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100754 · Cited by 118
Abitbol, S., Dahmani, R., Coulouarn, C., Ragazzon, B., Mlecnik, B., Senni, N., Savall, M., Bossard, P., Sohier, P., Drouet, V., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.12.018 · Cited by 117
Self-citationThe roles and regulation of TBX3 in development and disease
Khan, S. F., Damerell, V., Omar, R., Du Toit, M., Khan, M., Maranyane, H. M., Mlaza, M., Bleloch, J., Bellis, C., Sahm, B. D. B., et al. (2020) · Gene · doi:10.1016/j.gene.2019.144223 · Cited by 99
“Importantly, Renard et al. (2007) demonstrated that TBX3 is a direct transcriptional target of β-catenin/Tcf and that β-catenin mediated upregulation of TBX3 confers resistance to doxorubicin-induced apoptosis in U2OS osteosarcoma and HCT116 colorectal carcinoma cells.”
BackgroundTorre, C., Perret, C., & Colnot, S. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.11.004 · Cited by 106
Self-citationActivating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis
Dong, B., Lee, J.-S., Park, Y.-Y., Yang, F., Xu, G., Huang, W., Finegold, M. J., & Moore, D. D. (2015) · Nature Communications · doi:10.1038/ncomms6944 · Cited by 97
“The upregulated genes also include at least 10 known or candidate β -catenin targets, such as the ephrin receptor EFB2 43 and the T-Box transcriptional repressor TBX3 44 , and also the Wnt pathway components LEF1 and TCF7.”
Role of Cyclin D1 as a Mediator of c-Met– and β-Catenin–Induced Hepatocarcinogenesis
Patil, M. A., Lee, S. A., Macias, E., Lam, E. T., Xu, C., Jones, K. D., Ho, C., Rodríguez‐Puebla, M. L., & Chen, X. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2514 · Cited by 89
“Other targets of h-catenin include Tbx3 (38) and Gpr49 (39), both found to be up-regulated in liver tumors induced by hMet/h-catenin.”
BackgroundInfluentialWnt/β-Catenin Pathway in Hepatocellular Carcinoma Pathogenesis and Liver Physiology
Cavard, C., Colnot, S., Audard, V., Benhamouche, S., Finzi, L., Torre, C., Grimber, G., Godard, C., Terris, B., & Perret, C. (2008) · Future Oncology · doi:10.2217/14796694.4.5.647 · Cited by 94
Self-citationThe role and mechanism of claudins in cancer
Wang, D., Zhang, W., Galiullin, D., Yang, K., & Hu, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1051497 · Cited by 86
Genetics and signaling mechanisms of orofacial clefts
Reynolds, K., Zhang, S., Sun, B. H., Garland, M. A., Ji, Y., & Zhou, C. J. (2020) · Birth Defects Research · doi:10.1002/bdr2.1754 · Cited by 88
“Tcf/β-catenin can directly activate Tbx3, and while the mechanism is less well defined, Tbx3 mutant mice display full secondary CP (López et al., 2018; Renard et al., 2007).”
BackgroundYano, T., Yamazaki, Y., Adachi, M., Okawa, K., Fort, P., Uji, M., Tsukita, S., & Tsukita, S. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201009100 · Cited by 75
“Although the T-box proteins are thought to be regulated downstream of WNT and/or BMP signaling pathways (Renard et al., 2007), the signaling cascades that regulate the transcriptional activity or other events downstream of the T-box proteins are not fully understood.”
BackgroundKong, M., Li, L., Lou, Y.-M., Chi, H., & Wu, J. (2020) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2020.07.005 · Cited by 69
T-box transcription factors in cancer biology
Wansleben, S. M., Peres, J., Hare, S., Goding, C. R., & Prince, S. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.08.004 · Cited by 65
“[128] established that TBX3 mediates the pro-proliferative activity of the β-catenin signalling pathway in liver and colon cancer cells where the Wnt/β-catenin”
BackgroundDiverse functional networks of Tbx3 in development and disease
Washkowitz, A. J., Gavrilov, S., Begum, S., & Papaioannou, V. E. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1162 · Cited by 58
Relationship between apical junction proteins, gene expression and cancer
González‐Mariscal, L., Miranda, J., Gallego-Gutiérrez, H., Cano-Cortina, M., & Amaya, E. (2020) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2020.183278 · Cited by 55
The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
Li, J., Weinberg, M. S., Zerbini, L., & Prince, S. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-05-0273 · Cited by 56
Liang, B., Zhou, Y., Qian, M., Xu, M., Wang, J., Zhang, Y., Song, X., Wang, H., Lin, S., Ren, C., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.044 · Cited by 55
Latasa, M. U., Salis, F., Urtasun, R., García‐Irigoyen, O., Elizalde, M., Uriarte, I., Santamaría, M., Feo, F., Pascale, R. M., Prìeto, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052711 · Cited by 54
Perugorria, M. J., Castillo, J., Latasa, M. U., Goñi, S., Segura, V., Sangro, B., Prìeto, J., Avila, M. A., & Berasain, C. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2545 · Cited by 54
“Other antiapoptotic genes that were dependent on WT1 expression included the transcriptional repressor Tbx3 (28) and IGFBP1 (29), both recently described to enhance the survival of HCC cells, and the immediate early response gene X-1, a stress-inducible gene that codes for an intracellular membrane-associated protein…”
BackgroundInfluentialMicroRNA-137 represses Klf4 and Tbx3 during differentiation of mouse embryonic stem cells
Jiang, K., Ren, C., & Nair, V. D. (2013) · Stem Cell Research · doi:10.1016/j.scr.2013.09.001 · Cited by 55
“…notion, as Klf4, Tbx3, and LSD1 are highly expressed in undifferentiated ES cells and inmany forms of cancers (Fillmore et al., 2010; Hayami et al., 2011; Lim et al., 2010; Lomnytska et al., 2006; Lv et al., 2012; Renard et al., 2007; Schulte et al., 2009; Vance et al., 2005; Wei et al., 2010).”
BackgroundLi, Z., Ding, W., Sun, S., Li, J., Pan, J., Zhao, C., Wu, W., & Si, W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035754 · Cited by 55
“It has been shown that a consensus TCF4 binding element (TBE) is presented in the target genes of b-catenin/TCF4 complex [29,30,31].”
BackgroundEthanol extract of Fructus Ligustri Lucidi promotes osteogenesis of mesenchymal stem cells
Guo, L., Zhang, X., Zhang, J., Chan, C., Yew, D. T. W., He, M., Lin, M. C. M., Leung, P., & Kung, H. (2009) · Phytotherapy Research · doi:10.1002/ptr.2987 · Cited by 50
“The mRNA expressions of osteoblast differentiation regulators, including those involved in Wnt signaling (i.e., β-Catenin, Cyclin D1, MT1-MMP, OPG, TBX3), TGFβ signaling [i.e., TGFβ1, bone morphogenetic protein 2 (BMP2), BMP4], and transcription factors [i.e., MSX2, Runt-related transcription factor 2 (RUNX2), TAZ], w…”
BackgroundInfluentialTbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm
Waghray, A., Saiz, N., Jayaprakash, A. D., Freire, A. G., Papatsenko, D., Pereira, C.-F., Lee, D.-F., Brosh, R., Chang, B., Darr, H., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.05.009 · Cited by 50
“Expression of Tbx3 is regulated by Wnt signaling in mESCs (Kelly et al., 2011; Price et al., 2013) and cancer (Renard et al., 2007).”
BackgroundCanonical Wnt Signaling Induces a Primitive Endoderm Metastable State in Mouse Embryonic Stem Cells
Price, F. D., Yin, H., Jones, A., van IJcken, W. F. J., Grosveld, F. G., & Rudnicki, M. A. (2013) · Stem Cells · doi:10.1002/stem.1321 · Cited by 48
Tafrihi, M., & Sistani, R. N. (2017) · Nutrition and Cancer · doi:10.1080/01635581.2017.1320415 · Cited by 48
Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice
Dunnick, J. K., Pandiri, A. R., Merrick, B. A., Kissling, G. E., CUNNY, H. C., Mutlu, E., Waidyanatha, S., Sills, R. C., Hong, H. L. T., Ton, T.-V. T., et al. (2018) · Toxicology Reports · doi:10.1016/j.toxrep.2018.05.010 · Cited by 48
Upregulation of T‐cell factor‐4 isoform‐responsive target genes in hepatocellular carcinoma
Tomimaru, Y., Koga, H., Yano, H., de la Monte, S. M., Wands, J. R., & Kim, M. (2013) · Liver International · doi:10.1111/liv.12188 · Cited by 48
“In addition, there was no difference in the expression levels of known HCCassociated target genes such as LECT2 (12) and TBX3 (13) in TCF-4J or TCF-4K expressing HCC cell lines.”
BackgroundMixed ductal‐lobular carcinomas: evidence for progression from ductal to lobular morphology
Reed, A. E. M., Kutasovic, J. R., Nones, K., Saunus, J. M., Silva, L. M. D., Newell, F., Kazakoff, S. H., Melville, L. A., Jayanthan, J., Vargas, A. C., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5040 · Cited by 46
A WNT/p21 Circuit Directed by the C-Clamp, a Sequence-Specific DNA Binding Domain in TCFs
Hoverter, N. P., Ting, J.-H. T., Sundaresh, S., Baldi, P., & Waterman, M. L. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06769-11 · Cited by 45
“Many genes within this common subset are known Wnt target genes, such as ASCL2 (41), LGR5 (69), AXIN2 (53), cMYC (31), JAG1 (42), BMP4 (43), MET (11), TBX3 (65), and TNFRSF19 (TROY) (13) (for a complete list of genes, see Table S1).”
BackgroundOncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma
Hopkins, L., Rowe, I. A. C., & Houlihan, D. D. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1308785 · Cited by 54
Current Approaches in Hepatoblastoma—New Biological Insights to Inform Therapy
Wu, P. V., & Rangaswami, A. A. (2022) · Current Oncology Reports · doi:10.1007/s11912-022-01230-2 · Cited by 47
Expression of Tbx2 and Tbx3 in the developing hypothalamic–pituitary axis
Pontecorvi, M., Goding, C. R., Richardson, W. D., & Kessaris, N. (2008) · Gene Expression Patterns · doi:10.1016/j.gep.2008.04.006 · Cited by 40
The T-Box transcription factor 3 in development and cancer
Willmer, T., Cooper, A., Peres, J., Omar, R., & Prince, S. (2017) · BioScience Trends · doi:10.5582/bst.2017.01043 · Cited by 44
“have suggested that TBX3 is a direct target of this pathway in liver tumourigenesis (49).”
BackgroundInfluentialGu, Z., Wang, L., Dong, Q., Xu, K., Ye, J., Shao, X., Yang, S., Lu, C., Chang, C., Hou, Y., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2215744120 · Cited by 42
“Given that TBX3, a well-studied target downstream of the WNT/ β - catenin pathway and generally identified as one of the markers for zone 3 hepatocytes (41–43), was also markedly down-regulated in LYZ KO cells (Fig.”
The special stemness functions of Tbx3 in stem cells and cancer development
Dong, L., Lyu, X., Faleti, O. D., & He, M.-L. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.09.010 · Cited by 41
TWIST interacts with β-catenin signaling on osteosarcoma cell survival against cisplatin
Wu, J., Liao, Q., He, H., Zhong, D., & Yin, K. (2012) · Molecular Carcinogenesis · doi:10.1002/mc.21991 · Cited by 40
“As APC is required for degrading cytosolic (soluble) b-catenin, which is an important mediator of cell proliferation and survival [21], our findings provides a mechanistic explanation for this phenomenon.”
BackgroundUnique expression patterns of multiple key genes associated with the evolution of mammalian flight
Wang, Z., Dai, M., Wang, Y., Cooper, K. L., Zhu, T., Dong, D., Zhang, J., & Zhang, S. (2014) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.3133 · Cited by 39
“Studies have shown that Tbx3 can suppress apoptosis and promote cell proliferation in a variety of cell lines and organs [39–42], suggesting an important role in inhibiting the regression of forelimb interdigital tissues and promoting the growth of wing membranes in bats.”
BackgroundPerkhofer, L., Walter, K., Costa, I. G., Carrasco, M. C. R., Eiseler, T., Hafner, S., Genze, F., Zenke, M., Bergmann, W., Illing, A., et al. (2016) · Stem Cell Research · doi:10.1016/j.scr.2016.08.007 · Cited by 39
“, 2015) and hepatocellular carcinoma (Renard et al., 2007).”
BackgroundKatsuda, T., Hosaka, K., Matsuzaki, J., Usuba, W., Prieto‐Vila, M., Yamaguchi, T., Tsuchiya, A., Terai, S., & Ochiya, T. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.08.011 · Cited by 37
Tsai, K.-H., Hsien, H.-H., Chen, L.-M., et al. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.10.038 · Cited by 38
Mowla, S., Pinnock, R., Leaner, V. D., Goding, C. R., & Prince, S. (2011) · Biochemical Journal · doi:10.1042/bj20100886 · Cited by 38
Shan, Z., Yan, X., Yan, L.-L., Tian, Y., Meng, Q., Qiu, W., Zhang, Z., & Jin, Z. (2015) · Europe PMC (PubMed Central) · Cited by 37
Dong, L., Dong, Q., Chen, Y., Li, Y., Zhang, B., Zhou, F., Lyu, X., Chen, G. G., Lai, P., Kung, H.-F., et al. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0025-6 · Cited by 36
Activation of Wnt and Myc signaling in hepatoblastoma
Cairo, S. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/393 · Cited by 36
“Other targets such as cyclin D1 and the transcriptional repressor TBX3 might be involved in the growthpromoting and anti-apoptotic effects of Wnt in the liver, and both factors have been associated with unfavorable prognosis (27, 33, 34).”
BackgroundSelf-citationHumtsoe, J. O., Koya, E., Pham, E., Aramoto, T., Zuo, J., Ishikawa, T., & Kramer, R. H. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.11.011 · Cited by 36
Liu, J., Esmailpour, T., Shang, X., Gülşen, G., Liu, A., & Huang, T. (2011) · BMC Developmental Biology · doi:10.1186/1471-213x-11-65 · Cited by 34
“Wnt signaling has also been shown to play a major role in regulating mammary gland development [27].”
BackgroundAcquaah-Mensah, G. K., Malhotra, D., Vulimiri, M., McDermott, J., & Biswal, S. S. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002597 · Cited by 28
“TBX2 and its close relative, TBX3, negatively regulate cell cycle control genes and CDKNs, specifically CDKN2A, CDKN2B, and CDKN1A [51,53] and are often upregulated in several cancers [53,80,85].”
BackgroundBovo, S., Schiavo, G., Kazemi, H., Moscatelli, G., Ribani, A., Ballan, M., Bonacini, M., Prandi, M., Dall’Olio, S., & Fontanesi, L. (2021) · Animal Genetics · doi:10.1111/age.13109 · Cited by 34
“2004; Renard et al .”
BackgroundKranc, K. R., Oliveira, D. V., Armesilla-Diaz, A., Pacheco-Leyva, I., Matias, A. C., Escapa, A. L., Subramani, C., Wheadon, H., Trindade, M., Nichols, J., et al. (2014) · Stem Cells · doi:10.1002/stem.1889 · Cited by 30
The role of T-box genes in the tumorigenesis and progression of cancer
Chang, F., Xing, P., Song, F., Du, X., Wang, G., Chen, K., & Yang, J. (2016) · Oncology Letters · doi:10.3892/ol.2016.5296 · Cited by 31
“Using ChIP and reporter assays, a previous study identified TBX3 as a direct downstream regulatory target gene of the Wnt/ β -catenin signaling pathway that has been implicated in hepatocarcinogenesis (60).”
InfluentialZhang, J., He, M., Dong, Q., Xie, W., Chen, Y., Lin, M. C. M., Leung, P., Zhang, Y., & Kung, H. (2010) · Integrative Cancer Therapies · doi:10.1177/1534735410373921 · Cited by 28
“These findings were consistent with the previous reports in other cancer cells.(16) To demonstrate whether there were direct interactions between the effect of apoptosis and the downregulation of Tbx3 expression, we performed reporter assays.”
BackgroundResultWnt/β-Catenin Signaling Maintains the Mesenchymal Precursor Pool for Murine Sinus Horn Formation
Norden, J., Greulich, F., Rudat, C., Taketo, M. M., & Kispert, A. (2011) · Circulation Research · doi:10.1161/circresaha.111.245340 · Cited by 27
Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis
Lаgopati, N., Belogiannis, K., Angelopoulou, A., Papaspyropoulos, A., & Gorgoulis, V. G. (2021) · Biomolecules · doi:10.3390/biom11010086 · Cited by 30
“Moreover, TBX3, which was also identified as a downstream target of the Wnt pathway and a pivotal mediator of β-catenindependent proliferation and survival in liver tumorigenesis [91], was also found to be upregulated in breast cancer where it represses ARF expression by interacting with histone deacetylases [92].”
BackgroundWnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade
Jin, Y., Anbarchian, T., Wu, P., Sarkar, A., Fish, M., Peng, W. C., & Nusse, R. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203849119 · Cited by 26
“In hepatic tumor cells with activating β-catenin mutations, Tbx3 is overexpressed and mediates cell proliferation and survival (25).”
BackgroundGenetic and genomic analysis of hyperthelia in Brown Swiss cattle
Butty, A. M., Frischknecht, M., Gredler, B., Neuenschwander, S., Moll, J., Bieber, A., Baes, C. F., & Seefried, F. R. (2016) · Journal of Dairy Science · doi:10.3168/jds.2016-11420 · Cited by 25
“The protein encoded by TBX3 is also a downstream target of the canonical Wnt pathway (Renard et al., 2007).”
BackgroundThe Time-Resolved Genomic Impact of WNT/ β-Catenin Signaling
Pagella, P., Söderholm, S., Nordin, A., Zambanini, G., Ghezzi, V., Jauregi‐Miguel, A., & Cantù, C. (2022) · Cell Systems · doi:10.1016/j.cels.2023.06.004 · Cited by 29
Li, X., Ruan, X., Zhang, P., Yu, Y., Gao, M., Yuan, S., Zhao, Z., Yang, J., & Zhao, L. (2018) · Oncogene · doi:10.1038/s41388-017-0090-2 · Cited by 28
“catenin pathway induced TBX3 expression which, in turn, mediates β-catenin function [19].”
BackgroundShen, J., Lu, J., Sui, L., Wang, D., Yin, M., Hoffmann, I., Legler, A., & Pflugfelder, G. O. (2014) · Oncotarget · doi:10.18632/oncotarget.2426 · Cited by 22
“Importantly, small differences in TBX expression can correlate with drastic differences in patient survival [12].”
Ji, X., Chen, X., Zhang, B., Xie, M., Zhang, T., Luo, X., Liu, D., Feng, Y., Wang, Y., Sun, M., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02249-2 · Cited by 21
“It normally promotes HCC growth and metastasis regulated by the Wnt/ β-catenin pathway [18, 19].”
BackgroundLiu, Y., El‐Serag, H. B., Jiao, L., Lee, J., Moore, D. D., Franco, L. M., Tavakoli–Tabasi, S., Tsavachidis, S., Kuzniarek, J., Ramsey, D. J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084407 · Cited by 21
“TBX3 is a downstream target of the Wnt signaling pathway and a critical mediator of Wnt activities on cell proliferation and survival [28], with TBX3 overexpression well-documented in liver tumorigenesis [29].”
BackgroundWillmer, T., Cooper, A., Sims, D., Govender, D., & Prince, S. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.11 · Cited by 21
Lu, A., Kamkar, M., Chu, C., Wang, J., Gaudet, K., Chen, Y., Lin, L. E., Liu, W., Marbán, E., & Liang, W. (2019) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2019.09.019 · Cited by 20
Kavak, E., Najafov, A., Öztürk, N., Şeker, T., Cavusoglu, K., Aslan, T., Duru, A. D., Saygılı, T., Hoxhaj, G., Hiz, M. C., et al. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.05.021 · Cited by 22
Putative Breast Cancer Driver Mutations in TBX3 Cause Impaired Transcriptional Repression
Fischer, K. H., & Pflugfelder, G. O. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00244 · Cited by 21
Ballim, R. D., Mendelsohn, C. L., Papaioannou, V. E., & Prince, S. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-09-0790 · Cited by 20
“It has been shown to promote self-renewal of embryonic stem cells through up-regulation of the pluripotency factor Nanog (Ivanova et al., 2006; Niwa et al., 2009), and when coexpressed with Oct4, Sox2, and Klf4, Tbx3 improves the ability of induced pluripotent stem cells to colonize germ tissues…”
BackgroundKunasegaran, K., Ho, V., Chang, T. H. T., De Silva, D., Bakker, M. L., Christoffels, V. M., & Pietersen, A. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110191 · Cited by 18
“Tbx3 is likely to play a role in adult tissues as well, because Tbx3 has been implicated as an oncogene [23,24] and was found overexpressed in cell lines from several cancer types, including melanoma and hepatoma [24,25].”
BackgroundHealing Efficacy of fracture-targeted GSK3β inhibitor-loaded Micelles for Improved Fracture Repair
Low, S. A., Galliford, C. V., Jones‐Hall, Y., et al. (2017) · Nanomedicine · doi:10.2217/nnm-2016-0340 · Cited by 18
Sekine, S., Ogawa, R., Ojima, H., & Kanai, Y. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.03798.x · Cited by 17
How the pterosaur got its wings
Tokita, M. (2014) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12150 · Cited by 16
“Also, Tbx3 can promote cell proliferation in a variety of cell lines and organs (Carlson et al., 2002; Ito et al., 2005; Renard et al., 2007; Esmailpour & Huang, 2012), implying a role in promoting the growth of wing membranes in bats.”
BackgroundPluripotency Factors on Their Lineage Move
Weidgang, C. E., Seufferlein, T. T. W., Kleger, A., & Mueller, M. (2015) · Stem Cells International · doi:10.1155/2016/6838253 · Cited by 17
TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis
Wensing, L. A., & Campos, A. H. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.08.022 · Cited by 15
Zhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14
Study on the roles of β-catenin in hydrogen peroxide-induced senescence in human skin fibroblasts
Tian, L., Xie, H., Xiao, X., et al. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2011.01324.x · Cited by 14
The oncoprotein TBX3 is controlling severity in experimental arthritis
Sardar, S., Kerr, A., Vaartjes, D., Moltved, E. R., Karosiene, E., Gupta, R., & Andersson, Å. (2019) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1797-3 · Cited by 13
“Renard CA, Labalette C, Armengol C, Cougot D, Wei Y, Cairo S, et al. Tbx3 is a downstream target of the Wnt/β-catenin pathway and a critical mediator of β-catenin survival functions in liver cancer.”
BackgroundSmith, J. A. H., Mowla, S., & Prince, S. (2011) · Gene · doi:10.1016/j.gene.2011.07.013 · Cited by 13
The NF-Y complex negatively regulates Caenorhabditis elegans tbx-2 expression
Milton, A. C., Packard, A. V., Clary, L. M., et al. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.08.001 · Cited by 13
“These have identified Wnt/ß-catenin and BMP/Smad signaling pathways, the cell cycle regulators PML and E2F4, and the Nuclear Factor Y (NF-Y) complex as regulators of T-box gene expression (Martin et al., 2012; Renard et al., 2007; Smith et al., 2011; Teng et al., 2008; Zhang et al., 2011).”
Genetic and functional analysis of the TBX3 gene promoter in indirect inguinal hernia
Zhao, Z., Tian, W., Wang, L., Wang, H., Qin, X., Xing, Q., Pang, S., & Yan, B. (2014) · Gene · doi:10.1016/j.gene.2014.10.031 · Cited by 14
Feng, X., Yao, W., Zhang, Z., Yuan, F., Liang, L., Zhou, J., Liu, S., & Song, J. (2018) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504017x15145624664031 · Cited by 13
RetractedThe c-Myc/AKT1/TBX3 Axis Is Important to Target in the Treatment of Embryonal Rhabdomyosarcoma
Sims, D., Maranyane, H. M., Damerell, V., Govender, D., Isaacs, A. W., Peres, J., & Prince, S. (2020) · Cancers · doi:10.3390/cancers12020501 · Cited by 13
“For example, TBX3 bypasses senescence by repressing p14/p19ARF in breast cancer and promotes proliferation by repressing p21WAFI/CIPI/SDII (referred to as p21) in chondrosarcoma, p57KIP2 in papillary thyroid carcinoma, or phosphatase and tensin homologue (PTEN) in head and neck squamous cell carcinoma [24,28,30,31].”
BackgroundResultPflugfelder, G. O. (2008) · Journal of Neurogenetics · doi:10.1080/01677060802471619 · Cited by 13
“In several cases, TBX2/3 ampification correlated with the invasiveness, malignancy, or chemotherapy resistance of tumors (Adem et al., 2004; Lyng et al., 2006; Renard et al., 2007).”
BackgroundResultOverexpression of Tbx3 Predicts Poor Prognosis of Patients with Resectable Pancreatic Carcinoma
Wang, H.-C., Meng, Q.-C., Shan, Z.-Z., Yuan, Z., & Huang, X.-Y. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.4.1397 · Cited by 12
“In addition, accumulating evidence suggests that Tbx3 was also associated with clinicopathological features and poor prognosis in many malignant tumors (Renard et al., 2007; Rodriguez et al., 2008; Li et al., 2013; Du et al., 2014).”
BackgroundMonitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells
Song, M., Song, M., Choi, H., & Ryu, J. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1018-4 · Cited by 12
Aicher, S., Kakkanas, A., Cohen, L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-29078-2 · Cited by 12
Takeuchi, A., Asano, N., Imatani, A., Saito, M., Jin, X., Saito, M., Kanno, T., Hatta, W., Uno, K., Koike, T., et al. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0084 · Cited by 13
“…previous report which showed The intensified Wnt/ β -catenin signaling seen in the aged gastric organoids resulting from decreased Dkk3 expression led to induction of the transcription factor Tbx3, which is a Wnt/ β -catenin signaling target gene involved in the survival of liver cancer cells (33).”
Chen, Y., Yao, G., Sun, B., Zhang, C., Tommasini, S. M., & Insogna, K. L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.499210 · Cited by 12
“Relatively little is known about the transcriptional regulation of Tbx3 expression, although it has been reported that Wnt signaling and protein kinase C activation increase its expression (35, 36).”
BackgroundExpression of TBX3 in Hepatocellular Carcinoma and Its Clinical Implication
Li, Z., Wang, Y., Duan, S., Shi, Y., Li, S., Zhang, X., & Ren, J. (2018) · Medical Science Monitor · doi:10.12659/msm.909378 · Cited by 11
“model [25] and a cell experiment [26] have found that TBX3 is a downstream target of the Wnt/b-catenin pathway and an important mediator of b-catenin function in HCC.”
BackgroundNOTUM promotes thermogenic capacity and protects against diet-induced obesity in male mice
Guo, F., Seldin, M. M., Péterfy, M., Charugundla, S., Zhou, Z., Lee, S. D., Mouton, A., Rajbhandari, P., Zhang, W., Pellegrini, M. A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-95720-1 · Cited by 10
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
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.
A second model labelled each claim on 2026-10-23 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
Are you an author, or do you see a problem with this page? Request a review
