Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Thesis Charles Marusak 3.0.pdf (2.5 MB)

ETD Abstract Container

Abstract Header

MT1-MMP: TARGETING THE CENTER OF MELANOMA METASTASIS, GROWTH AND TREATMENT RESISTANCE

Marusak, Charles
http://orcid.org/0000-0001-5395-2484
http://rave.ohiolink.edu/etdc/view?acc_num=case1548327646756039

Abstract Details

2019, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
In the past decade advances in cancer research have dramatically improved melanoma prognosis. Metastatic melanoma, once considered untreatable, now takes advantage of a plethora of treatment strategies and lays at the vanguard of many experimental techniques such as targeted therapy and immune therapy. Due to its adaptability, melanoma has proven to be highly prone to developing treatment resistance and no strategy has yet been developed to combat late stage metastatic melanoma without a high risk of resistance and reoccurrence. Membrane type 1 matrix metalloproteinase (MT1-MMP) is a protease that is ubiquitously expressed and necessary for development. As a collagenase, its primary role is the digestion of collagen in the extracellular matrix (ECM). More recently it has been shown to have roles through direct cleavage or through its downstream effects in angiogenesis, epithelial mesenchymal transition (EMT), invasion, migration, survival and cell growth. This study aims to investigate MT1-MMP as a viable target for inhibition in melanoma metastasis and growth. It will also investigate melanomas resistance to BRAF targeted therapy, identify a novel mechanism of resistance and present a new strategy to counteract this resistance. It will be shown that melanoma upregulates MT1-MMP expression in response to BRAF inhibition and that this upregulation can cause an increase in integrin-beta1 (ITGB1) signaling. It will also be shown that knockdown of MT1-MMP mitigates this integrin BRAF inhibition resistance and that MT1-MMP inhibition is a promising treatment option for countering melanoma treatment resistance.
Hung-Ying Kao, Ph.D. (Committee Chair)
Barbara Bedogni, Ph.D. (Advisor)
Eli Bar, Ph.D. (Committee Member)
David Samols, Ph.D. (Committee Member)
175 p.
Biochemistry; Biology; Biomedical Research; Cellular Biology; Chemistry; Medicine; Oncology
MMP14; MT1-MMP; Melanoma; Cancer; BRAF; Resistance; Treatment; Vemurafenib; Integrin; MMP2; Collagen; Targeted Therapy; FAK; ND322; Metastasis; Growth; Oncology; Medicine; Inhibitor

Recommended Citations

Citations

  • Marusak, C. (2019). MT1-MMP: TARGETING THE CENTER OF MELANOMA METASTASIS, GROWTH AND TREATMENT RESISTANCE [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1548327646756039

    APA Style (7th edition)

  • Marusak, Charles. MT1-MMP: TARGETING THE CENTER OF MELANOMA METASTASIS, GROWTH AND TREATMENT RESISTANCE. 2019. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1548327646756039.

    MLA Style (8th edition)

  • Marusak, Charles. "MT1-MMP: TARGETING THE CENTER OF MELANOMA METASTASIS, GROWTH AND TREATMENT RESISTANCE." Doctoral dissertation, Case Western Reserve University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1548327646756039

    Chicago Manual of Style (17th edition)

case1548327646756039
312
© 2019, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.