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The role of TEX19 in growth and maintenance of colorectal cancer stem-like cells

Planells-Palop, Vicente (2016) The role of TEX19 in growth and maintenance of colorectal cancer stem-like cells. PhD thesis, Prifysgol Bangor University.

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Abstract

Cancer Stem-like Cells (CSC) are believed to be responsible for local relapse and metastasis of tumours and may also be the cells that are responsible for resistance to therapies. As such, it is of fundamental importance to study the molecular mechanisms involved in generating cells with properties of CSCs. Cancer Testis Antigen (CTA) genes are a group of genes, with generally unknown function, whose expression is restricted to the testis (and fetal ovary and placenta) in normal individuals, but are also expressed in a wide variety of malignant tumour types. CTAs are potentially of great immunotherapeutic importance since the testis is an immune privileged tissue meaning that the immune system does not recognise antigens normally present in this site. TEX19 (Testis Expressed 19) is a cancer/testis (CT) gene, and the expression of the murine orthologue was first detected in the testis and ovary. Since then, TEX19 has been shown to be expressed in adult human testis (spermatogonia) and also in human and mouse embryonic stem (ES) cells. The function of this gene remains unknown although several studies suggest that it maintains the self-renewal potential and pluripotency of germ and ES cells. More recently, TEX19 has been reported as a regulator of the expression of transposable elements (TE). TEs are DNA sequences which can change their position within the genome; therefore they can cause deleterious mutations, gene disruption and chromosome rearrangements that may lead to cancer. Here we show that human TEX19 is present in spermatogonias in adult tissues, but it is found in a wide range of cancer tissues. For the first time we show that TEX19 is a dynamic protein that can shuttle between the nucleus and the cytoplasm in cancer cells. In addition, TEX19 enables proliferation in colorectal cancer cell lines in vivo and in vitro, by suppressing a quiescent-like state in these cells. Specifically, in TEX19 knockdown conditions, cell cycle analysis shows an accumulation of cells in S-phase. Depletion of TEX19 causes alterations in the expression pattern of a subset of genes, which most are linked to RNA/DNA processing, cell communication or regulation of cell cycle and proliferation. Moreover, our work confirms the influence of TEX19 in the expression of human endogenous retrovirus (HERV), a subclass of transposable elements (TE); suggesting that TEX19 might be a TE expression/activity regulator. Finally, our preliminary work has also identified potential TEX19-interacting partners. All these results taken together suggest that TEX19 might be a key regulatory factor in cancer, with potential applications as a biomarker or target.

Item Type: Thesis (PhD)
Additional Information: Third Party Copyright Content
Subjects: Degree Thesis
Departments: College of Health and Behavioural Sciences > School of Medical Sciences
Degree Thesis
Date Deposited: 30 Sep 2016 14:34
Last Modified: 30 Sep 2016 14:34
URI: http://e.bangor.ac.uk/id/eprint/8095
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