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Lavik Dissertation.pdf (9.64 MB)

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A Collaborative Role for Neuronal-Wiskott Aldrich Syndrome protein and Mammalian Diaphanous-related Formins during Invadopodia Formation and Invasion

Lavik, Kari I
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461964353

Abstract Details

2016, Doctor of Philosophy, University of Toledo, Biology (Cell-Molecular Biology).
Invadopodia are actin-rich protrusions that extend from the ventral side of invasive cancer cells into the underlying matrix at the tumor-stroma margin. These finger-like projections initially harness the force of actin polymerization to drive cellular protrusion into the surrounding membrane or tissue barrier. Invadopodia later secrete degradative enzymes to catalyze the invasion of cancer cells away from the primary tumor site. The branched actin nucleating Arp2/3 complex and its nucleation promoting factor, neuronal-Wiskott Aldrich Syndrome protein (N-WASp), are established drivers of invadopodia protrusion formation. However, the non-branched actin nucleating proteins mammalian Diaphanous (mDia)-related formins also localize to these invasive structures and remain largely unstudied. While investigating mDia formin involvement in invadopodia formation, we found that the formin mDia1 significantly induced early invadopodia formation. As N-WASp-Arp2/3 requires pre-existing linear actin filaments to achieve maximum polymerization, we proposed that mDia1 closely associates with N-WASp-Arp2/3 to provide these non-branched filaments. Immunofluorescence and co-immunoprecipitation studies revealed that mDia1 and N-WASp complexed through the mutual binding adaptor protein, diaphanous interacting protein (DIP/SPIN90). Upon loss of DIP, this binding triplex was disrupted. By elucidating the mechanistic underlying mDia formins requirement during early invadopodia formation, we can better design compounds to block invadopodia formation thereby decreasing cancer invasion and metastasis.
Kathryn Eisenmann (Advisor)
239 p.
Biology; Biomedical Research; Cellular Biology

Recommended Citations

Citations

  • Lavik, K. I. (2016). A Collaborative Role for Neuronal-Wiskott Aldrich Syndrome protein and Mammalian Diaphanous-related Formins during Invadopodia Formation and Invasion [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461964353

    APA Style (7th edition)

  • Lavik, Kari. A Collaborative Role for Neuronal-Wiskott Aldrich Syndrome protein and Mammalian Diaphanous-related Formins during Invadopodia Formation and Invasion. 2016. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461964353.

    MLA Style (8th edition)

  • Lavik, Kari. "A Collaborative Role for Neuronal-Wiskott Aldrich Syndrome protein and Mammalian Diaphanous-related Formins during Invadopodia Formation and Invasion." Doctoral dissertation, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461964353

    Chicago Manual of Style (17th edition)

toledo1461964353
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© 2016, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.
Release 3.2.12