Exploring the effect of genetic calpain disruption on cell migration, invasion, drug sensitivity, and metastasis in triple negative breast cancer
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Authors
Cockburn, Samantha
Date
2024-08-28
Type
thesis
Language
eng
Keyword
Triple Negative Breast Cancer , Calpain
Alternative Title
Abstract
Triple-negative breast cancer is an aggressive subtype of breast cancer that is associated with high rates of metastasis, which remains incurable. Neoadjuvant chemotherapies, like paclitaxel, have been reported to promote spread to secondary sites. Calpains are a family of calcium-activated proteases that have emerged as a potential target in triple-negative breast cancer. Calpains cleave substrates involved in various cell signalling pathways associated with tumourigenesis and metastasis. Based on these established roles for calpain, I aimed to further characterise the effects of calpain knockout on migration, invasion, tumour growth, and paclitaxel-induced metastasis in a mouse model of triple-negative breast cancer. I also explored the role of collapsin response mediator protein 2, a calpain substrate and microtubule-binding protein, in paclitaxel treatment. I hypothesised that calpain-deficient cells would be less migratory, invasive, and metastatic than wildtype cells and that calpain knockout would disrupt neoadjuvant paclitaxel-induced metastasis. I also hypothesised that over-expression of collapsin response mediator protein 2, would synergise with calpain knockout to sensitise triple-negative breast cancer cells to paclitaxel and impede migration and invasion in vitro. By understanding calpain’s role in metastasis, we aim to improve the efficacy of existing chemotherapeutics by combining them with pharmacological calpain inhibitors, thus expediting the development of much needed therapies for triple-negative breast cancer.
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Attribution-NonCommercial-NoDerivatives 4.0 International
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.
Attribution-NonCommercial-NoDerivatives 4.0 International