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Cited by 44Developmental Biology and Gene RegulationCancer-related Molecular PathwaysGenomics and Chromatin Dynamics

The T-Box transcription factor 3 in development and cancer

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Willmer, Tarryn, Cooper, Aretha, Peres, Jade, Omar, Rehana, Prince, Sharon·2017·BioScience Trends
DOI 10.5582/bst.2017.01043
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Abstract

T-box factors comprise an archaic family of evolutionary conserved transcription factors that regulate patterns of gene expression essential for embryonic development. The T-box transcription factor 3 (TBX3), a member of this family, is expressed in several tissues and plays critical roles in, among other structures, the heart, mammary gland and limbs and haploinsufficiency of the human TBX3 gene is the genetic basis for the autosomal dominant disorder, ulnar-mammary syndrome. Overexpression of TBX3 on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and a number of sarcoma subtypes. Furthermore, there is strong evidence that TBX3 promotes oncogenesis by impacting proliferation, tumour formation, metastasis as well as cell survival and drug resistance. More recently, TBX3 was however shown to also have tumour suppressor activity in fibrosarcomas and thus its functions in oncogenesis appear to be context dependent. Identification of the upstream regulators of TBX3 and the molecular mechanism(s) underpinning its oncogenic roles will make valuable contributions to cancer biology.

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  • TBX3 acts as a tumor suppressor in β-catenin-driven HCC.

    “However, TBX3 acts as a tumor suppressor in other tumor entities, including β-catenin-driven HCC [18, 21, 22].”

    From Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma (2024) · cites this paper as [18]

    Section 2.4.1 says that in β-catenin-driven liver tumours, TBX3 promotes proliferation, tumour formation and survival—the opposite of a tumour-suppressor role. Section 2.3.4 describes a tumour-suppressor role in transformed fibroblast and fibrosarcoma models, not in β-catenin-driven HCC. (LLM, conf=0.91)

    Checked by a reasoning model — may be wrong.

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  • TBX3 is often up-regulated in tumorigenesis and promotes tumor cell proliferation and metastasis, especially during BRAF/MAPK induced tumorigenesis.

    “Recently, the oncogenic function of TBX3 draws attention, where TBX3 is often up-regulated in tumorigenesis and promotes tumor cell proliferation and metastasis, especially during BRAF/MAPK induced tumorigenesis12–16.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [13]

    Section 2.3 says TBX3 is overexpressed in many cancers and can promote proliferation, tumour formation and invasion; section 2.3.2 links elevated TBX3 to metastasis and describes BRAF V600E–driven TBX3 promoting melanoma-cell invasion. The paper does not establish that TBX3 especially promotes proliferation and metastasis during BRAF/MAPK-induced tumorigenesis. Section 2.3.1 also reports that TBX3 can reduce proliferation in melanoma cells. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • TBX3 has also been shown to function as a tumor suppressor in fibrosarcoma and liver cancer.

    “TBX3 has also been shown to function as a tumor suppressor in fibrosarcoma and liver cancer, suggesting that the role of TBX3 is cancer-specific 67,68.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [67]

    Section 2.3.4 states that TBX3 behaves as a tumour suppressor in transformed fibroblast and fibrosarcoma cells. The liver-cancer part is not supported: section 2.3.2 instead reports that TBX3 contributes to tumour formation in hepatoma carcinoma cells. The paper therefore supports a context-dependent role, but not the claimed tumour-suppressor role in liver cancer. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • TBX3 behaves as a tumor suppressor or oncoprotein across cancer.

    “TBX3 behaves as a tumor suppressor or oncoprotein across cancer.”

    From Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma (2024) · cites this paper as [18]

  • TBX3 is critical in embryonic stem cell maintenance, lineage specification, and embryogenic organ formation, and its up- or down-regulation leads to aberrant regulation of cell fate/proliferation and different malignancies.

    “As a critical factor in embryonic stem cells maintenance, lineage specification, and embryogenic organ formation, TBX3 expression is finely controlled, with its up or down-regulation leading to aberrant regulation of cell fate/proliferation and different malignancies.13.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [13]

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References 100 · Cited by 44

Research works printed but not linked: 81

  1. Papaioannou VE. The T-box gene family: Emerging roles in development, stem cells and cancer. Development. 2014; 141:3819-3833.
  2. Wilson V, Conlon FL. The T-box family. Genome Biol. 2002; 3:3008.1-3008.
  3. Lingbeek ME, Jacobs JJ, van Lohuizen M. The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. J Biol Chem. 2002; 277:26120-26127.
  4. van den Boogaard M, Wong LY, Tessadori F, Bakker ML, Dreizehnter LK, Wakker V, Bezzina CR, t Hoen PA, Bakkers J, Barnett P, Christoffels VM. Genetic variation in T-box binding element functionally affects SCN5A/ SCN10A enhancer. J Clin Invest. 2012; 122:2519-2530.
  5. Papaioannou VE. T-box genes in development: From hydra to humans. Int Rev Cytol. 2001; 207:1-70.
  6. Packham EA, Brook JD. T-box genes in human disorders. Hum Mol Genet. 2003; 12:R37-R44.
  7. Wansleben S, Peres J, Hare S, Goding CR, Prince S. T-box transcription factors in cancer biology. Biochim Biophys Acta. 2014; 1846:380-391.
  8. Agulnik SI, Garvey N, Hancock S, Ruvinsky I, Chapman DL, Agulnik I, Bollag R, Papaioannou V, Silver LM. Evolution of mouse T-box genes by tandem duplication and cluster dispersion. Genetics. 1996; 144:249-254.
  9. Bamshad M, Lin RC, Law DJ, Watkins WC, Krakowiak PA, Moore ME, Franceschini P, Lala R, Holmes LB, Gebuhr TC, Bruneau BG, Schinzel A, Seidman JG, Seidman CE, Jorde LB. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Gen. 1997; 16:311-315.
  10. Campbell C, Goodrich K, Casey G, Beatty B. Cloning and Mapping of a Human Gene (TBX2) Sharing a Highly Conserved Protein Motif with the Drosophila omb Gene. Genomics. 1995; 28:255-260.
  11. Law DJ, Gebuhr T, Garvey N, Agulnik SI, Silver LM. Identification, characterization and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family. Mamm Genome. 1995; 6:793-797.
  12. Fan W, Huang X, Chen C, Gray J, Huang T. TBX3 and its isoform TBX3+2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines. Cancer Res. 2004; 64:5132-5139.
  13. Bamshad M, Le T, Watkins WS, et al. The spectrum of mutations in TBX3: Genotype/Phenotype relationship in ulnar-mammary syndrome. Am J Hum Genet. 1999; 64:1550-1562.
  14. Hoogaars WM, Barnett P, Rodriguez M, Clout DE, Moorman AF, Goding CR, Christoffels VM. TBX3 and its splice variant TBX3 + exon 2a are functionally similar. Pigment Cell Melanoma Res. 2008; 21:379-387.
  15. Zhao D, Wu Y, Chen K. Tbx3 isoforms are involved in pluripotency maintaining through distinct regulation of Nanog transcriptional activity. Biochem Biophys Res Commun. 2014; 444:411-414.
  16. Kumar PP, Franklin S, Emechebe U, Hu H, Moore B, Lehman C, Yandell M, Moon AM. TBX3 regulates splicing in vivo: A novel molecular mechanism for Ulnar- mammary syndrome. PLoS Genet. 2014; 10:e1004247.
  17. Boogerd CJJ, Wong LYE, van den Boogaard M, Bakker ML, Tessadori F, Bakkers J, 't Hoen PAC, Moorman AF, Christoffels VM, Barnett P. Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43. Cell Mol Life Sci. 2011; 68:3949-3961.
  18. Coll M, Seidman JG, Muller CW. Structure of the DNA- bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome. Structure. 2002; 10:343-356.
  19. Lu J, Li X-P, Dong Q, Kung H-f, He M-L. TBX2 and TBX3: The special value for anticancer drug targets. Biochim Biophys Acta. 2010; 1806:268-274.
  20. Chapman DL, Garvey N, Hancock S, Alexiou M, Agulnik SI, Gibson-Brown JJ, Cebra-Thomas J, Bollag RJ, Silver LM, Papaioannou VE. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996; 206:379-390.
  21. Washkowitz AJ, Gavrilov S, Begum S, Papaioannou VE. Diverse functional networks of Tbx3 in development and disease. Wiley Interdiscip Rev Syst Biol Med. 2012; 4:273-283.
  22. Davenport TG, Jerome-Majewska LA, Papaioannou VE. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development. 2003; 130:2263-2273.
  23. Jerome-Majewska LA, Jenkins GP, Ernstoff E, Zindy F, Sherr CJ, Papaioannou VE. Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Dev Dyn. 2005; 234:922-933.
  24. Bishop AE, Buttery LD, Polak JM. Embryonic stem cells. J Pathol. 2002; 197:424-429.
  25. Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, Schafer X, Lun Y, Lemischka IR. Dissecting self-renewal in stem cells with RNA interference. Nature. 2006; 442:533-538.
  26. Jiang K, Ren C, Nair VD. MicroRNA-137 represses Klf4 and Tbx3 during differentiation of mouse embryonic stem cells. Stem Cell Res. 2013; 11:1299-1313.
  27. Cheng X, Ying L, Lu L, Galvão AM, Mills JA, Lin HC, Kotton DN, Shen SS, Nostro MC, Choi JK, Weiss MJ, French DL, Gadue P. Self-Renewing Endodermal Progenitor Lines Generated from Human Pluripotent Stem Cells. Cell Stem Cell. 2012; 10:371-384.
  28. Kartikasari AE, Zhou JX, Kanji MS, Chan DN, Sinha A, Grapin-Botton A, Magnuson MA, Lowry WE, Bhushan A. The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation. Embo J. 2013; 32:1393-1408.
  29. Price FD, Yin H, Jones A, van Ijcken W, Grosveld F, Rudnicki MA. Canonical Wnt signaling induces a primitive endoderm metastable state in mouse embryonic stem cells. Stem Cells. 2013; 31:752-764.
  30. Waghray A, Saiz N, Jayaprakash AD, Freire AG, Papatsenko D, Pereira CF, Lee DF, Brosh R, Chang B, Darr H, Gingold J, Kelley K, Schaniel C, Hadjantonakis AK, Lemischka IR. Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm. Stem Cell Reports. 2015; 5:97-110.
  31. Han J, Yuan P, Yang H, Zhang J, Soh BS, Li P, Lim SL, Cao S, Tay J, Orlov YL, Lufkin T, Ng H-H, Tam W-L, Lim B. Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature. 2010; 463:1096- 1100.
  32. Declercq J, Sheshadri P, Verfaillie CM, Kumar A. Zic3 enhances the generation of mouse induced pluripotent stem cells. Stem Cells Dev. 2013; 22:2017-2025.
  33. Bakker ML, Boukens BJ, Mommersteeg MT, Brons JF, Wakker V, Moorman AF, Christoffels VM. Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system. Circ Res. 2008; 102:1340-1349.
  34. Falco G, Lee SL, Stanghellini I, Bassey UC, Hamatani T, Ko MS. Zscan4: A novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells. Dev Biol. 2007; 307:539-550.
  35. Dan J, Li M, Yang J, Li J, Okuka M, Ye X, Liu L. Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells. Sci Rep. 2013; 3:3492.
  36. Weinberger L, Ayyash M, Novershtern N, Hanna JH. Dynamic stem cell states: Naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Bio. 2016; 17:155- 169
  37. Miao ZF, Liu XY, Xu HM, Wang ZN, Zhao TT, Song YX, Xing YN, Huang JY, Zhang JY, Xu H, Xu YY. Tbx3 overexpression in human gastric cancer is correlated with advanced tumor stage and nodal status and promotes cancer cell growth and invasion. Virchows Archiv. 2016; 469:505-513.
  38. Yarosh W, Barrientos T, Esmailpour T, Lin L, Carpenter PM, Osann K, Anton-Culver H, Huang T. TBX3 is overexpressed in breast cancer and represses p14 ARF by interacting with histone deacetylases. Cancer Res. 2008; 68:693-699.
  39. Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. 2007; 35:495-516.
  40. Carlson H, Ota S, Song Y, Chen Y, Hurlin PJ. Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation. Oncogene. 2002; 21:3827-3835.
  41. Zhang JF, He ML, Qi D, Xie WD, Chen YC, Lin MC, Leung PC, Zhang YO, Kung HF. Aqueous extracts of Fructus Ligustri Lucidi enhance the sensitivity of human colorectal carcinoma DLD-1 cells to doxorubicin-induced apoptosis via Tbx3 suppression. Integr Cancer Ther. 2011; 10:85-91.
  42. Willmer T, Peres J, Mowla S, Abrahams A, Prince S. The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2. Cell Cycle. 2015; 14:3173-3183.
  43. Platonova N, Scotti M, Babich P, Bertoli G, Mento E, Meneghini V, Egeo A, Zucchi I, Merlo GR. TBX3, the gene mutated in ulnar-mammary syndrome, promotes growth of mammary epithelial cells via repression of p19ARF, independently of p53. Cell Tissue Res. 2007; 328:301-316.
  44. Willmer T, Hare S, Peres J, Prince S. The T-box transcription factor TBX3 drives proliferation by direct repression of the p21WAF1 cyclin-dependent kinase inhibitor. Cell Division. 2016; 11:6.
  45. Burgucu D, Guney K, Sahinturk D, Ozbudak IH, Ozel D, Ozbilim G, Yavuzer U. Tbx3 represses PTEN and is over- expressed in head and neck squamous cell carcinoma. BMC Cancer. 2012; 12:481.
  46. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009; 4:127-150.
  47. Peres J, Davis E, Mowla S, Bennett DC, Li JA, Wansleben S, Prince S. The Highly Homologous T-Box Transcription Factors, TBX2 and TBX3, Have Distinct Roles in the Oncogenic Process. Genes Cancer. 2010; 1:272-282.
  48. Ballim RD, Mendelsohn C, Papaioannou VE, Prince S. The ulnar-mammary syndrome gene, Tbx3, is a direct target of the retinoic acid signaling pathway, which regulates its expression during mouse limb development. Mol Bio Cell. 2012; 23:2362-2372.
  49. Chen ZH, Lu GM, Ji TH. Expression of TBX3 mRNA and its role in the pathogenesis and metastasis of breast cancer. Nan Fang Yi Ke Da Xue Xue Bao. 2009; 29:87-89 (in Chinese).
  50. Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, Kuperwasser C. Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci U S A. 2010; 107:21737- 21742.
  51. Mowla S, Pinnock R, Leaner VD, Goding CR, Prince S. PMA-induced up-regulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration. Biochem J. 2011; 433:145-153.
  52. Canel M, Serrels A, Frame MC, Brunton VG. E-cadherin- integrin crosstalk in cancer invasion and metastasis. J Cell Sci. 2013; 126:393-401.
  53. Rodriguez M, Aladowicz E, Lanfrancone L, Goding CR. Tbx3 Represses E-Cadherin Expression and Enhances Melanoma Invasiveness. Cancer Res. 2008; 68:7872- 7881.
  54. Boyd SC, Mijatov B, Pupo GM, Tran SL, Gowrishankar K, Shaw HM, Goding CR, Scolyer RA, Mann GJ, Kefford RF, Rizos H, Becker TM. Oncogenic B-RAF(V600E) signaling induces the T-Box3 transcriptional repressor to repress E-cadherin and enhance melanoma cell invasion. J Invest Dermatol. 2013; 133:1269-1277.
  55. Yano T, Yamazaki Y, Adachi M, Okawa K, Fort P, Uji M, Tsukita S, Tsukita S. Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. J Cell Biol. 2011; 193:319-332.
  56. Humtsoe JO, Koya E, Pham E, Aramoto T, Zuo J, Ishikawa T, Kramer RH. Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells. Exp Cell Res. 2012; 318:379-390.
  57. Du HF, Ou LP, Yang X, Song XD, Fan YR, Tan B, Luo CL, Wu XH. A new PKCalpha/beta/TBX3/E-cadherin pathway is involved in PLCepsilon-regulated invasion and migration in human bladder cancer cells. Cell Signal. 2014; 26:580-593.
  58. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5:275-284.
  59. Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T. Chemical genomic screening for methylation- silenced genes in gastric cancer cell lines using 5-aza-2'- deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006; 97:64-71.
  60. Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F, Saikali S, Hamlat A, Riffaud L, Menei P, Quillien V, Mosser J. DNA methylation in glioblastoma: Impact on gene expression and clinical outcome. BMC Genomics. 2010; 11:701.
  61. White-Al Habeeb NMA, Ho LT, Olkhov-Mitsel E, Kron K, Pethe V, Lehman M, Jovanovic L, Fleshner N, van der Kwast T, Nelson CC, Bapat B. Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer. Oncotarget. 2014; 5:7858- 7869.
  62. Kandimalla R, van Tilborg AA, Kompier LC, Stumpel DJ, Stam RW, Bangma CH, Zwarthoff EC. Genome- wide analysis of CpG island methylation in bladder cancer identified TBX2, TBX3, GATA2, and ZIC4 as pTa- specific prognostic markers. Eur Urol. 2012; 61:1245- 1256.
  63. Beukers W, Kandimalla R, Masius RG, Vermeij M, Kranse R, van Leenders GJ, Zwarthoff EC. Stratification based on methylation of TBX2 and TBX3 into three molecular grades predicts progression in patients with pTa-bladder cancer. Mod Pathol . 2015; 28:515-522.
  64. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004; 20:781-810.
  65. Tsai KH, Hsien HH, Chen LM, Ting WJ, Yang YS, Kuo CH, Tsai CH, Tsai FJ, Tsai HJ, Huang CY. Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-beta activation to enhance protein degradation and attenuate nuclear translocation of beta-catenin. Food Chem. 2013; 138:278-285.
  66. Cavard C, Audebourg A, Letourneur F, Audard V, Beuvon F, Cagnard N, Radenen B, Varlet P, Vacher- Lavenu MC, Perret C, Terris B. Gene expression profiling provides insights into the pathways involved in solid pseudopapillary neoplasm of the pancreas. J Pathol. 2009; 218:201-209.
  67. Arendt LM, St. Laurent J, Wronski A, Caballero S, Lyle SR, Naber SP, Kuperwasser C. Human breast progenitor cell numbers are regulated by WNT and TBX3. PLoS One. 2014; 9:e111442.
  68. Katoh M, Nakagama H. FGF receptors: Cancer biology and therapeutics. Med Res Rev. 2014; 34:280-300.
  69. Eblaghie MC, Song S-J, Kim J-Y, Akita K, Tickle C, Jung H-S. Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos. J Anat. 2004; 205:1-13.
  70. Marengo B, De Ciucis C, Ricciarelli R, Pronzato MA, Marinari UM, Domenicotti C. Protein Kinase C: An attractive target for cancer therapy. Cancers. 2011; 3:531- 567.
  71. Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu TC, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorg Med Chem. 2014; 22:673-683.
  72. Garattini E, Paroni G, Terao M. Retinoids and breast cancer: New clues to increase their activity and selectivity. Breast Cancer Res. 2012; 14:111-111.
  73. Tumpel S, Sanz-Ezquerro JJ, Isaac A, Eblaghie MC, Dobson J, Tickle C. Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development. Dev Biol. 2002; 250:251-262.
  74. Imamura T, Hikita A, Inoue Y. The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer. 2012; 19:118-124.
  75. Tian F, DaCosta Byfield S, Parks WT, Yoo S, Felici A, Tang B, Piek E, Wakefield LM, Roberts AB. Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Res. 2003; 63:8284-8292.
  76. Nitulescu GM, Margina D, Juzenas P, Peng Q, Olaru OT, Saloustros E, Fenga C, Spandidos D, Libra M, Tsatsakis AM. Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use. Int J Oncol. 2016; 48:869-885.
  77. Samuels Y, Ericson K. Oncogenic PI3K and its role in cancer. Current Opinion in Oncology. 2006; 18:77-82.
  78. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: Variations on a theme. Oncogene. 2008; 27:5497- 5510.
  79. Tomita Y, Morooka T, Hoshida Y, Zhang B, Qiu Y, Nakamichi I, Hamada K, Ueda T, Naka N, Kudawara I, Aozasa K. Prognostic significance of activated AKT expression in soft-tissue sarcoma. Clin Cancer Res. 2006; 12:3070-3077.
  80. Valkov A, Kilvaer TK, Sorbye SW, Donnem T, Smeland E, Bremnes RM, Busund L-T. The prognostic impact of Akt isoforms, PI3K and PTEN related to female steroid hormone receptors in soft tissue sarcomas. J Transl Med. 2011; 9:200-200.
  81. Gonzalez E, McGraw TE. The Akt kinases: Isoform specificity in metabolism and cancer. Cell Cycle. 2009; 8:2502-2508. 100. Fortier AM, Asselin E, Cadrin M. Functional specificity of Akt isoforms in cancer progression. Biomol Concepts. 2011; 2:1-11. (Received February 27, 2017; Revised May 23, 2017; Accepted May 25, 2017)

Authors
Willmer, T., Cooper, A., Peres, J., Omar, R., & Prince, S.
Affiliations
University of Cape Town (ZA)
ORCID
Venue
BioScience Trends
Publisher
International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA)
Published
2017
Volume
11
Issue
3
Pages
254-266
ISSN
  • 1881-7815 (ISSN-L)
  • 1881-7823
DOI
10.5582/bst.2017.01043
OpenAlex
W2621251683
Cited by
44
References
100
Citations by year
2026: 3 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 1
FWCI
0.31
Type
journal article
Language
en
Open access
Locations
  • BioScience Trends (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation
  • Cancer Association of South Africa
  • Harry Crossley Foundation
  • University of Cape Town
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
TBX3, T-box transcription factor, embryonic development, ulnar-mammary syndrome, haploinsufficiency, cancer, carcinogenesis, tumour suppressor, metastasis, drug resistance, melanoma, fibrosarcoma, limb development, heart development, mammary gland development
MeSH terms
Animals, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Developmental, T-Box Domain Proteins, Embryonic Development, Mice

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