Post-graduate theses
Current Record: 4962 of 6549
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| Identifier |
000397274 |
| Title |
Role of the oncogene KDM2B in the epigenetic regulation of the cytoskeleton |
| Alternative Title |
Ο ρόλος του ογκογονιδίου KDM2B στην επιγενετική ρύθμιση του κυτταροσκελετού |
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Author
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Ζαχαροπούλου, Νεφέλη Ζ.
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Thesis advisor
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Στουρνάρας, Χρήστος
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Reviewer
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Καμπράνης, Σωτήρης
Ζάχος, Γιώργος
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| Abstract |
Cancer can evolve from a combination of epigenetic and genetic abnormalities resulting in dysregulated gene expression and function. In cancer, many physiological cellular activities are altered; epithelial cells lose their polarity and cell-cell adhesion, and gain migratory and invasive properties, in a process that involves a dramatic reorganization of the cytoskeleton, accompanied by the formation of membrane protrusions required for invasive growth. Many molecules have been shown to be implicated in cancer. Several lines of evidence suggest that alterations in chromatin regulators have been linked to deregulated cytoskeletal functions and cell-cell adhesion, but the mechanisms behind these processes are now beginning to emerge. Focusing on the role of KDM2B and based on our hypothesis that in cancer, epigenetic alterations frequently result in the deregulation of the mechanisms maintaining normal cytoskeleton organization and cell-cell adhesion function, we will try to understand how chromatin regulation and epigenetic mechanisms influence the onset and progression of cancer.
In DU145 and HCT116 cells expressing either an shKDM2B or overexpressing KDM2B, we found that the expression levels of several proteins involved in the cytoskeleton and in cell-cell adhesion are altered. Especially, the expression levels of EZH2 upon depletion of KDM2B were downregulated and the expression levels of the cell adhesion protein E-cadherin upregulated. Also, we saw a significant change on the expression levels of the RhoGTPases family proteins, RHOA, RHOB, RHOC, RAC1 and CDC42. Especially, in both cell lines, the expression levels of RhoA, RhoB, RhoC and Cdc42 were downregulated upon knockdown of KDM2B, whereas Rac1 was upregulated. The altered expression levels of several proteins of the cytoskeleton and of adhesion junction upon overexpression or knockdown of KDM2B lead us to propose a model for increased migration rate for the cells that overexpress KDM2B. This was confirmed in a wound-healing assay and in a proliferation assay. Based on our results, we can conclude that KDM2B may directly regulate major signaling molecules controlling cellular physiology and may promote somehow motility and invasion.
By elucidating the underlying mechanism of how histone demethylase KDM2B interconnect with cytoskeleton organization and cell to cell adhesion, it will be established a basic framework of how epigenetic regulation controls the structure and function of the cytoskeleton and adhesion junction and how deregulated chromatin regulators can impact basic aspects of cellular physiology. This research is highly innovative, as it constitutes the first focused effort towards elucidation of the cross-regulation between chromatin and the cytoskeleton. Using the mechanism of cytoskeleton regulation by KDM2B as an example, this project addresses fundamental questions and creates significant added value by developing important tools and expertise in this area. Future studies on the cancer epigenome and its regulation will redefine our understanding of the cancer cell and may reveal new targets for therapeutic intervention.
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| Language |
English |
| Subject |
Cancer |
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Histone demethylase |
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Απομεθυλάση ιστονών |
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Καρκίνος |
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Κυτταροσκελετός |
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Ογκονίδιο |
| Issue date |
2015-11-20 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
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Type of Work--Post-graduate theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/f/0/0/metadata-dlib-1448273655-697025-32040.tkl
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| Views |
275 |
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