• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Elucidation of the Role of CD44 Receptor and its Intracellular Domain in the Progression of Prostate Cancer

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Senbanjo_umaryland_0373D_11051.pdf
    Size:
    1.805Mb
    Format:
    PDF
    Download
    Author
    Senbanjo, Linda Temilade
    Advisor
    Chellaiah, Meenakshi A.
    Date
    2019
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United States partially due to metastatic spread to secondary sites in the bone, brain, lymph nodes and visceral organs. Here, we examine the mechanisms that can facilitate PCa progression/metastasis. CD44 is a multifunctional receptor that functions in tumorigenesis and cancer progression. Recent studies point to CD44 cleavage product; CD44 Intracellular Domain (ICD) as the fragment responsible for transcription of metastasis-related genes (MRGs). Using knockdown and overexpression strategy, we 1) determine the effect of androgen receptor (AR) and CD44 expression on stemness characteristics of PCa cells (PC3), 2) characterize CD44-ICD interaction with RUNX2 in PC3 cells and 3) determine the specificity of interaction of CD44-ICD sequences with RUNX2 and its contribution to PCa progression. We show SOX2 expression is high at mRNA and protein levels of bone metastatic PC3 cells that are AR-negative. Additionally, CD44 regulates the expression of SOX2 and knockdown of SOX2, or CD44 resulted in decrease of cell migration which was reversed with the re-expression of AR. To examine the contribution of CD44-ICD to the tumorigenic potential of PCa cells, we characterized CD44-ICD expression in PCa cells then determined its interaction with RUNX2, a transcription factor also known to promote tumorigenesis. We show the interaction of CD44-ICD/RUNX2 in the nucleus and overexpression of RUNX2 resulted in increased cell migration and tumorsphere formation via the upregulation of MRGs. Consistently, generation and overexpression of CD44-ICD-FL and CD44-ICD carboxyl-terminal deletion constructs resulted in increased interaction with RUNX2 in the nucleus with greater specificity for interacting with constructs: FL and D1 to D3. Likewise, these constructs show an increase in the expression of OPN and MMP-9 genes. However, CD44-ICD-FL, as well as D1 to D3 constructs, shows more specificity to the promoter of MMP-9 in CHIP assay analyses. This also corresponds with the expression levels of MMP-9 protein. These findings not only suggest the specificity of CD44-ICD function towards the expression of MMP-9 but also metastasis relevant events including migration and tumorigenesis. These also implicate CD44-ICD as a novel therapeutic target in cancer cells that express CD44.
    Description
    2019
    Molecular Medicine
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    CD44
    CD44-ICD
    MMP9
    Metastasis
    Prostate—Cancer
    Matrix Metalloproteinase 9
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/9571
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.