Li, Shun
(2023)
Investigating effect of galectin-3 on protease secretion in human colon cancer cells.
PhD thesis, University of Liverpool.
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Abstract
Proteases are enzymes that are responsible for proteolysis of proteins in living organisms. They regulate multiple biological processes. The catalytic reaction of proteases is irreversible therefore the level of proteases is tightly regulated in physiological condition. In epithelial cancer, the expression and secretion of proteases are often dysregulated, resulting in increased cancer cell growth, invasion, migration, angiogenesis and metastasis. Galectin-3, a β-galactoside-binding protein expressed by many types of human cells, is often found to be overexpressed in various cancers. Extracellular galectin-3 is known to interact with many cell surface molecules and promotes multiple steps in cancer progression and metastasis. This project investigated the hypothesis that galectin-3-mediated promotion of cancer progression and metastasis might be associated with regulation of protease expression in cancer cells. Various experiments were used in this study to assess the effect of galectin-3 on protease expression and secretion in human colon cancer cells and the effect of galectin-3-mediated protease expression and secretion on cancer cell invasion and signalling. It was found that galectin-3 induces the secretion of a number of proteases in colon cancer cells in an autocrine and paracrine way. Higher galectin-3 expression and secretion by cancer cells was associated with higher protease secretion. It was also found that this galectin-3-induced secretion of proteases directly promoted colon cancer cell invasion, disrupted epithelial integrity and caused leakage of the epithelial monolayer. The underlying mechanism of galectin-3 inducing protease secretion is likely via activation of PYK2/GSK3 signalling, at least for cathepsin B in this study. These discoveries provide insight into the impact of galectin-3 and galectin-3-induced protease secretion on cancer cell behaviour in cancer progression and metastasis and may aid future development of novel therapeutic strategies for cancer.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health and Life Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 Feb 2024 16:37 |
| Last Modified: | 02 Feb 2024 16:37 |
| DOI: | 10.17638/03176818 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3176818 |
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