Regulation of organogenesis and stem cell properties by T-box transcription factors

Takashima, Yasuo; Suzuki, Atsushi

doi:10.1007/s00018-013-1305-5

Cited by 29 publications

(24 citation statements)

References 134 publications

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“…It is also possible to induce stem cell properties by genetic or other manipulation of fibroblast cells in vitro to obtain induced pluripotent stem cells (iPSCs). Given their pivotal role in many developmental processes, it is perhaps not surprising that several T-box genes have been implicated either as stem cell factors that promote self-renewal or as differentiation factors that drive the differentiation of stem or progenitor cells (Takashima and Suzuki, 2013) (Fig. 1 and Fig.…”

Section: T-box Genes and Stem Cell Biologymentioning

confidence: 99%

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The T-box gene family: emerging roles in development, stem cells and cancer

2014

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The T-box family of transcription factors exhibits widespread involvement throughout development in all metazoans. T-box proteins are characterized by a DNA-binding motif known as the T-domain that binds DNA in a sequence-specific manner. In humans, mutations in many of the genes within the T-box family result in developmental syndromes, and there is increasing evidence to support a role for these factors in certain cancers. In addition, although early studies focused on the role of T-box factors in early embryogenesis, recent studies in mice have uncovered additional roles in unsuspected places, for example in adult stem cell populations. Here, I provide an overview of the key features of T-box transcription factors and highlight their roles and mechanisms of action during various stages of development and in stem/progenitor cell populations.

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Section: T-box Genes and Stem Cell Biologymentioning

confidence: 99%

“…A comprehensive review of the older literature and work on other species can be found in earlier reviews (e.g. Morley et al, 2009;Naiche et al, 2005;Papaioannou, 2001;Papaioannou and Silver, 1998;Showell et al, 2004;Smith, 1999;Takashima and Suzuki, 2013;Wardle and Papaioannou, 2008).…”

Section: Introductionmentioning

confidence: 99%

The T-box gene family: emerging roles in development, stem cells and cancer

2014

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“…T-box 3 (Tbx3), a member of the T-box transcription factor family, is widely expressed in the nervous system, heart, lungs and pancreas (4). Accumulating evidence has demonstrated that Tbx3 is involved in the developmental process by binding to the T-box motif with a 20-24 nucleotide palindromic sequence, the T-site, or half of the sequence in the promoters of target genes (5). A mutation of Tbx3 was demonstrated to be closely associated with the pluripotency of embryonic stem cells and the invasiveness of cancer (6).…”

Section: Introductionmentioning

confidence: 99%

T-box 3 overexpression is associated with poor prognosis of non-small cell lung cancer

Jiang

Zhang

2017

Oncology Letters

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Abstract. T-box 3 (Tbx3), a member of the T-box transcription factor family, serves a crucial role in embryonic development and cancer progression. Previous studies have demonstrated the clinical significance of Tbx3 in numerous types of cancer. However, the expression level and pathological function of Tbx3 in non-small cell lung cancer (NSCLC) are unknown. To the best of our knowledge, the present study provided the first evidence demonstrating the clinicopathological significance of Tbx3 in NSCLC. Tbx3 was revealed to be overexpressed in NSCLC cell lines and tissues obtained from patients with NSCLC by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Downregulation of Tbx3 by Tbx3-specific short hairpin RNA decreased cell proliferation in NSCLC cell lines, but there was a slight increase in the cell population of the G 1 phase. Furthermore, depletion of Tbx3 expression significantly decreased the cell migration distance. In addition, overexpression of Tbx3 was notably associated with tumor size, tobacco smoking status, tumor-node-metastasis stage and differentiation. These results demonstrated the importance of Tbx3 in the pathological progression of NSCLC and may serve as a potential therapeutic target for NSCLC.

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“…These genes have a role in regulating the proliferation and differentiation of tissue-specific stem and progenitor cells during organogenesis (5,6). Previous studies have indicated that altered T-box gene expression may be associated with human cancer (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma

et al. 2016

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Abstract. TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype. IntroductionOvarian cancer is the fourth most common type of cancer in the female genital tract, but has the highest mortality rate of all gynecological tumors. Ovarian carcinoma accounts for >90% of cases of ovarian cancer and may arise from relatively pluripotent cells of the coelomic epithelium or 'modified mesothelium' that covers the ovary (1). The coelomic epithelium is the mesodermal-derived epithelial lining of the intraembryonic coelom that invaginates to give rise to the mülllerian ducts, the primordia for the epithelia of the fallopian tube, the endometrium and the endocervix (1). There is now compelling evidence that certain carcinomas can also originate from the fallopian tubes and the endometriosis (1,2). Ovarian carcinoma are a heterogeneous group of neoplasms that exhibit a wide range of tumor morphologies and clinical manifestations (2). According to the World Health Organization classification, the most common tumor subtypes are serous, endometrioid and mucinous, and are characterized by their morphological resemblance to various mucosal tissues of the female reproductive tract (3). Cytogenetic and molecular analysis indicates that multiple genetic and epigenetic changes are involved in the pathogenesis of ovarian carcinoma (2,4); however, it remains unclear how these alterations lead to the development of ovarian cancer. Better understanding of the molecular mechanisms responsible for the diffe...

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Regulation of organogenesis and stem cell properties by T-box transcription factors

Cited by 29 publications

References 134 publications

The T-box gene family: emerging roles in development, stem cells and cancer

The T-box gene family: emerging roles in development, stem cells and cancer

T-box 3 overexpression is associated with poor prognosis of non-small cell lung cancer

Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma

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