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dc.contributor.authorShapovalov, Ivanen
dc.date.accessioned2020-07-14T16:47:51Z
dc.date.available2020-07-14T16:47:51Z
dc.identifier.urihttp://hdl.handle.net/1974/27965
dc.description.abstractBreast cancer is the most frequently diagnosed women’s cancer in Canada. Average patient survival rates are high, but they are significantly reduced for those patients whose cancer reaches stage IV – metastatic disease. This study investigated the roles of calpain-1 and calpain-2 in metastatic breast cancer. Genetic knockout of CAPN1, CAPN2, and CAPNS1 genes allowed us to analyze the functions of these two calpain isoforms in the MDA-MB-231 triple negative breast cancer model cell line and to determine which isoform is responsible for the CAPNS1-knockdown related cancer cell phenotypes seen previously. We used the panel of knockout and rescue cell lines for in vitro studies and showed that both calpain isoforms play roles in protective effects against select chemotherapeutics, suggesting that calpain inhibition could enhance the efficacy of these commonly used breast cancer therapeutics. We also showed that genetic disruption of calpain-1 reduces the in vitro cell migration rate on collagen substrates. Our in vivo studies provide evidence that calpain-1 and calpain-2 have essential non-redundant roles in the metastatic process, suggesting that inhibition of either isoform could have therapeutic benefits by reducing the metastatic potential of breast cancer. I also discuss future studies aimed at identification and characterization of calpain-1 and calpain-2 specific physiological substrates with mechanistic relevance to the observed phenotypes and describe a biosensor to screen for allosteric inhibitors of calpain-1 and calpain-2.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectCalpainen
dc.subjectTriple Negative Breast Canceren
dc.subjectMetastasisen
dc.titleElucidating Isoform Specific Roles of Calpain-1 and Calpain-2 in Breast Canceren
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorGreer, Peter A.
dc.contributor.departmentPathology and Molecular Medicineen
dc.embargo.termsThe reason for restricting the thesis is to protect rights to the structure of biosensor constructs described in the thesis which will be used in a future application for a patent arising from the research.en
dc.embargo.liftdate2025-07-13T21:49:40Z
dc.degree.grantorQueen's University at Kingstonen


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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
Except where otherwise noted, this item's license is described as Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada