T-box transcription factors in cancer biology

Wansleben, Sabina; Peres, Jade; Hare, Shannagh; Goding, Colin R.; Prince, Sharon

doi:10.1016/j.bbcan.2014.08.004

Cited by 53 publications

(58 citation statements)

References 166 publications

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“…This indicated that TBX3 was a transcriptional repressor and identified regions 567-623 and 123-200 as repression domains, which the authors called R1 and R2, respectively. Indeed, TBX3 was subsequently shown to transcriptionally repress p14ARF/p19ARF, p21WAF1, Nppa, E-cadherin, and phosphatase and tensin homolog (PTEN) (7). Furthermore, when R1 or R2 were fused to the VP16 (herpes simplex virus protein 16) activation domain and tested in similar experiments, R1 but not R2, was able to override the VP16 activation domain and to repress transcriptional activity (17).…”

Section: Tbx3 Gene and Protein Structurementioning

confidence: 99%

“…Indeed, TBX3 co-operated with the Myc oncogene to transform MEFs, where it promoted the bypass of Myc induced apoptosis through the downregulation of p19ARF and p53 levels (47). In addition, TBX3 has been shown to inhibit apoptosis in rat bladder hyperplastic epithelial cells and TBX3 knockdown increased apoptosis in rat bladder carcinoma cells (7). TBX3 was also linked to protecting cells against anoikis which is a form of apoptosis that occurs when anchorage dependent cells become detached from the surrounding extracellular matrix and its bypass is associated with epithelial mesenchymal transition (EMT).…”

Section: Tbx3 In Senescence Apoptosis and Proliferationmentioning

confidence: 99%

“…Senescence is an irreversible/permanent exit from the cell cycle and Tbx3 can bypass this process and consequently immortalise mouse embryonic fibroblasts (MEFs) and ST.HdhQ111 striatal cells through either directly binding or repressing a T-element in the initiator of p19ARF/p14ARF or by recruiting HDAC 1, 2, 3 and 5 to epigenetically silence its promoter (7,45). A recent study by Kumar et al demonstrated that TBX3 can also bypass senescence by indirectly repressing p16INK4a (22).…”

Section: Tbx3 In Senescence Apoptosis and Proliferationmentioning

confidence: 99%

“…TBX3 is overexpressed in a range of carcinomas (breast, pancreatic, melanoma, liver, gastric, lung, head and neck, ovarian and bladder) and sarcomas (chondrosarcoma, fibrosarcoma, liposarcoma, rhabdomyosarcoma and synovial sarcoma) (7,43,44). Importantly, there is substantial evidence that this overexpression contributes to the oncogenic process at multiple levels including the bypass of senescence and apoptosis as well as the promotion of proliferation, tumour formation and invasion ( Figure 2).…”

Section: Tbx3 and Cancermentioning

confidence: 99%

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The T-Box transcription factor 3 in development and cancer

Willmer

Cooper

Peres

et al. 2017

BST

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Section: Tbx3 Gene and Protein Structurementioning

confidence: 99%

Section: Tbx3 In Senescence Apoptosis and Proliferationmentioning

confidence: 99%

Section: Tbx3 In Senescence Apoptosis and Proliferationmentioning

confidence: 99%

Section: Tbx3 and Cancermentioning

confidence: 99%

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The T-Box transcription factor 3 in development and cancer

Willmer

Cooper

Peres

et al. 2017

BST

Self Cite

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“…Several studies have revealed aberrations of TBX genes in inherited human disorders, such as TBX1 mutation in DiGeorge syndrome, TBX3 mutation in Ulnar -Mammary syndrome, TBX5 mutation in Holt -Oram syndrome, and TBX22 mutation in cleft palate with ankyloglossia 11) . In addition, recent studies have also found that TBX genes may be associated with cancer development in various malignant tumors 12) . TBX2 and TBX3, which are downstream targets of the Wnt/betacatenin pathway, are frequently mutated in ovarian cancer and are amplified in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

<i>TBX19</i> is overexpressed in colorectal cancer and associated with lymph node metastasis

Ando

Saito

Imai

et al. 2017

FJMS

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The T -box 19 (TBX19) gene encodes a transcription factor characterized by a highly conserved DNA -binding motif (T -box). Recent studies have revealed that TBX19 has been identified as one of the genes activated by KRAS mutations, and is upregulated in colon adenoma. These results indicate that TBX19 may work as an oncogene in colorectal cancer (CRC). However, the expression and role of TBX19 have yet to be investigated. Here, we investigated TBX19 mRNA and protein expressions in colon cancer cells or surgically resected CRC. We found that TBX19 mRNA expression was significantly increased in tumorous tissues compared to that in non -tumorous tissues, and increased TBX19 mRNA expression was associated with positive lymph node metastasis in our cohort. The expression of TBX19 mRNA was not correlated with that of TBX19 protein in tissue sample taken from the CRC patients. Moreover, TBX19 showed positive staining even in the normal colonic tissues and the adjacent non -tumorous tissues. These results suggest that the expression of TBX19 protein is not correlated with the expression of TBX19 mRNA. In addition, our results promote further investigations into the impact of TBX19 upregulation on colorectal carcinogenesis, as well as the underlying mechanisms.

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T‐Box Genes: Developmental Functions in Mammals

Papaioannou

2017

Encyclopedia of Life Sciences

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Transcription factors encoded by the T‐box gene family control key functions throughout development in all metazoans. The DNA (deoxyribonucleic acid)‐binding domain is highly conserved. There are 17 genes in mouse and human, all with diverse functional roles from early embryogenesis through organogenesis and tissue homeostasis. The same gene may function in different tissues and at different stages such that mutation phenotypes can be complex. Most T‐box mutations display heterozygous defects, indicating dose sensitivity. Several T‐box genes affect pluripotency and differentiation in the pre‐ and early postimplantation embryo; limb outgrowth and differentiation is a major developmental area affected by T‐box genes as is the heart, nervous system, immune system and many other organs and tissues. T‐box gene loss‐of‐function mutations in humans cause major developmental syndromes such as ulnar‐mammary and Holt–Oram syndrome, and other abnormalities are increasingly being attributed to alteration in T‐box gene function, including the association with many types of cancer. Key Concepts T‐box genes code for transcription factors with diverse roles in development through regulation of a variety of downstream target genes. They comprise an ancient gene family present in all metazoans as well as nonmetazoan lineages, defined by a conserved DNA‐binding motif. In vertebrates, T‐box genes play diverse and key roles in specification, differentiation and development of most organ systems. Mutations in T‐box genes result in complex birth defects and/or neonatal lethality and usually show effects in heterozygotes and homozygotes. Multiple tissues may be affected by the same T‐box gene, and multiple T‐box genes may affect the same tissue at the same or different times in development. Mutation or misregulation of T‐box genes is associated with a large variety of human cancers. Little information is available about the role of T‐box genes in adult organisms.

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T-box transcription factors in cancer biology

Cited by 53 publications

References 166 publications

The T-Box transcription factor 3 in development and cancer

The T-Box transcription factor 3 in development and cancer

<i>TBX19</i> is overexpressed in colorectal cancer and associated with lymph node metastasis

T‐Box Genes: Developmental Functions in Mammals

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