Exploring Isoform-specific Roles of Calpain-1 and Calpain-2 in Breast Cancer Metastasis Promoting Cellular Functions
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Authors
Min, Jung
Date
Type
thesis
Language
eng
Keyword
Breast Cancer , Calpain-1 , Calpain-2 , Cell Migration , Cell Invasion
Alternative Title
Abstract
Breast cancer (BC) is the most diagnosed cancer among Canadian women. Among the breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits the poorest survival outcome, likely due to its heterogeneity and lack of defined therapeutic targets. Detection of localized BC at an early stage often leads to a curative outcome. However, disease progression to metastatic dissemination is the major cause of high mortality rates, underscoring the value of novel approaches targeting the metastatic process. Calpain proteases have emerged as potential novel therapeutic targets in TNBC, due to their involvement in regulating cell migration and invasion, two processes required for the metastatic potential. This thesis explored independent and non-redundant roles of calpain-1 and calpain-2 isoforms in cellular functions promoting TNBC metastasis. Using a panel of capn1, capn2, and capns1 CRISPR-Cas9 genetic knockout (KO) and lentiviral rescue MDA-MB-231 human TNBC cell lines, cell migration and invasion were investigated in vitro. Absence of either calpain-1 or calpain-2 reduced the migratory potential of MDA-MB-231 cells, where calpain-2 disruption had the greatest effect in reducing the average speed. Calpain-2 was also identified as the dominant isoform regulating the invasive potential of MDA-MB-231 cells. Collectively, our observations suggest isoform-specific roles of calpain-1 and calpain-2 in BC metastasis, and provide insights on calpain proteases as novel targets that may be applied alone or synergistically with conventional therapies to treat metastatic BC.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Copying and Preserving Your Thesis
This 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.
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This 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.