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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“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 · see citing works
“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 · see citing works
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 63 · see citing works
“[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 <i>Tbx3</i> 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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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 53 · see citing works
“…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 53 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
Tafrihi, M., & Sistani, R. N. (2017) · Nutrition and Cancer · doi:10.1080/01635581.2017.1320415 · Cited by 49 · see citing works
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 · see citing works
Upregulation of T‐cell factor‐4 isoform‐responsive target genes in hepatocellular carcinoma
Tomimaru, Y., Koga, H., Yano, H., et al. (2013) · Liver International · doi:10.1111/liv.12188 · Cited by 47 · see citing works
“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 · see citing works
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 · see citing works
“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 45 · see citing works
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 44 · see citing works
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 · see citing works
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 · see citing works
“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 41 · see citing works
“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 · see citing works
TWIST interacts with β-catenin signaling on osteosarcoma cell survival against cisplatin
Wu, J., Liao, Q., He, H., et al. (2012) · Molecular Carcinogenesis · doi:10.1002/mc.21991 · Cited by 40 · see citing works
“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. Y. (2014) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.3133 · Cited by 38 · see citing works
“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 · see citing works
“, 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 36 · see citing works
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 · see citing works
Mowla, S., Pinnock, R., Leaner, V. D., Goding, C. R., & Prince, S. (2011) · Biochemical Journal · doi:10.1042/bj20100886 · Cited by 38 · see citing works
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 · see citing works
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 · see citing works
Activation of Wnt and Myc signaling in hepatoblastoma
Cairo, S. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/393 · Cited by 36 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 30 · see citing works
“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 · see citing works
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 29 · see citing works
“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 · see citing works
“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 · see citing works
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 29 · see citing works
“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 · see citing works
“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 · see citing works
“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 26 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
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 21 · see citing works
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 21 · see citing works
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 20 · see citing works
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 19 · see citing works
“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 · see citing works
“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 · see citing works
Sekine, S., Ogawa, R., Ojima, H., & Kanai, Y. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.03798.x · Cited by 17 · see citing works
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 · see citing works
“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 16 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
Aicher, S., Kakkanas, A., Cohen, L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-29078-2 · Cited by 12 · see citing works
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 12 · see citing works
“…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., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.499210 · Cited by 12 · see citing works
“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 · see citing works
“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 · see citing works
- 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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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.
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