• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    The Role of Mechanical Cues and Metabolism in Breast Cancer Cell Migration

    Mosier, Jenna
    0000-0002-1671-744X
    : http://hdl.handle.net/1803/18506
    : 2023-07-11

    Abstract

    Breast cancer metastasis is initiated when cells break through basement membrane and migrate through the surrounding tissue before spreading throughout the body to colonize secondary sites. The primary tumor microenvironment, composed primarily of collagen, imparts mechanical challenges upon cancer cells that regulate their migration ability, metabolism, and metastatic potential. In this dissertation, I investigate the interplay of confinement and cellular metabolism in breast cancer cell migration using an engineered collagen microtrack platform. Cancer cells migrating through the primary tumor microenvironment must navigate confined spaces in the tissue. Using our collagen microtrack platform, we find that breast cancer cells in confinement exhibit increased velocity and cell-generated matrix strains. Further, cells maintain increased velocity even after transitioning from a confined to an unconfined region, indicating that cells can be conditioned in confinement to alter future migration ability. We find that this priming in confinement correlates with increased mitochondrial localization at the leading edge of the cell, and that disrupting focal adhesion formation by knocking out vinculin inhibits memory and mitochondrial localization. We next investigate the role of glucose metabolism and epithelial-to-mesenchymal transition (EMT) in migration through collagen microtracks. We find that modulating glucose metabolism by inhibiting glycolysis or oxidative phosphorylation can shift EMT status to alter migration ability. Further, inducing EMT can modulate cell metabolism to affect migration ability, indicating a link between cancer cell bioenergetics and EMT. Finally, we establish cellular metabolic phenotype as a stable, heritable trait of cancer cells that can determine cell response to mechanical cues and migration ability. Specifically, higher energy cells with increased ATP:ADP ratios exhibit increased velocity in confinement compared to lower energy cells. Taken together, this work identifies a key link between metabolism and confined migration in breast cancer cells and highlights potential avenues for therapeutics to treat breast cancer metastasis.
    Show full item record

    Files in this item

    Icon
    Name:
    MOSIER-DISSERTATION-2023.pdf
    Size:
    4.526Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy