Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells
Abstract Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon can...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05789-x |
| _version_ | 1797845743094988800 |
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| author | Shun Li David Mark Pritchard Lu-Gang Yu |
| author_facet | Shun Li David Mark Pritchard Lu-Gang Yu |
| author_sort | Shun Li |
| collection | DOAJ |
| description | Abstract Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/β signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer. |
| first_indexed | 2024-04-09T17:43:51Z |
| format | Article |
| id | doaj.art-5b06190b06684cf7be425e0d44fd1674 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T17:43:51Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-5b06190b06684cf7be425e0d44fd16742023-04-16T11:26:36ZengNature Publishing GroupCell Death and Disease2041-48892023-04-0114411110.1038/s41419-023-05789-xGalectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cellsShun Li0David Mark Pritchard1Lu-Gang Yu2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of LiverpoolDepartment of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of LiverpoolDepartment of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of LiverpoolAbstract Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/β signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.https://doi.org/10.1038/s41419-023-05789-x |
| spellingShingle | Shun Li David Mark Pritchard Lu-Gang Yu Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells Cell Death and Disease |
| title | Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| title_full | Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| title_fullStr | Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| title_full_unstemmed | Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| title_short | Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| title_sort | galectin 3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells |
| url | https://doi.org/10.1038/s41419-023-05789-x |
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