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IMPORTANCE OF ALPHA-CATENIN AND CELL-CELL INTERACTIONS IN HAIR FOLLICLE STEM CELLS HOMEOSTASIS
by
Surbhi
A Thesis Presented to the
FACULTY OF THE USC VITERBI SCHOOL OF ENGINEERING
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOMEDICAL ENGINEERING)
December 2010
Copyright 2010 Surbhi
Object Description
| Title | Importance of alpha-catenin and cell-cell interactions in hair follicle stem cells homeostasis |
| Author | Surbhi |
| Author email | surbhi@usc.edu; rajsurbhi@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-10-08 |
| Advisor (committee chair) | Kobielak, Agnieszka |
| Advisor (committee member) |
D'Argenio, David Lu, Zhong-Lin |
| Abstract | In multi-cellular organisms, cell–cell contacts that are mediated by classical cadherins have essential roles in many fundamental processes, such as morphogenesis, maintenance of tissue integrity, wound healing and cell polarity. Furthermore, there is overwhelming evidence that the adherens junctions (AJs) are also an important tumor and/or invasion suppressor. Alpha-catenin is the protein that connects E-cadherin–beta-catenin complexes with the actin cytoskeleton. Although it was previously considered to be a solely structural protein, it has become increasingly clear that alpha-catenin has a central role in both assembling the actin cytoskeleton and regulating its dynamics at cell–cell junctions thus regulating cell polarity. Cell-polarity mechanisms are responsible not only for the diversification of cell shapes but also for regulation of the asymmetric cell divisions of stem cells that are crucial for their correct self-renewal and differentiation. Disruption of cell polarity is a hallmark of cancer. Although null mutations in alpha-E-catenin have been associated with epithelial cancers it has been usually assumed that perturbations in cell–cell adhesion are late rather than early steps in carcinogenesis, and that they are preceded by mutations in cell-cycle-regulated genes that lead to uncontrolled growth. In our previous experiments we have shown that loss of alpha-catenin in the whole epidermis during embryonic development results in formation of squamous cell carcinoma.; To understand the origin of squamous cell carcinoma as well as focus on the role of cell adhesion and polarity on the maintenance of quiescence stem cell niche and transition toward tumor development, we disrupted in inducible manner the alpha-catenin gene specifically in the hair follicle stem cells using alpha-catenin flox/flox and Keratin15-CrePR mice. The results highlighted that alpha-catenin ablation leads to loss structural tissue integrity in hair follicles, leading to tumor-like cellular populations, which are highly proliferative but lack differentiation. This suggests that knockout of alpha-catenin might lead to asymmetric division in stem cells. This indeed proves that alpha-catenin has an important role to play in the maintenance of adherence junctions. The findings also signify the use of alpha-catenin as a prognostic marker for squamous cell carcinomas. |
| Keyword | alpha-catenin; hair follicle; stem cell; homeostasis; squamous cell carcinoma |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3498 |
| Rights | Surbhi |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-NLN-3883 |
| Archival file | uscthesesreloadpub_Volume51/etd-NLN-3883.pdf |
Description
| Title | Page 1 |
| Full text | IMPORTANCE OF ALPHA-CATENIN AND CELL-CELL INTERACTIONS IN HAIR FOLLICLE STEM CELLS HOMEOSTASIS by Surbhi A Thesis Presented to the FACULTY OF THE USC VITERBI SCHOOL OF ENGINEERING UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOMEDICAL ENGINEERING) December 2010 Copyright 2010 Surbhi |
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