Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade
Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apop...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/40322 |
| _version_ | 1848755838567579648 |
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| author | Zhuo, J. Tan, E. Yan, B. Tochhawng, L. Jayapal, M. Koh, S. Tay, H. Maciver, S. Hooi, S. Salto-Tellez, M. Kumar, Alan Prem Goh, Y. Lim, Y. Yap, C. |
| author_facet | Zhuo, J. Tan, E. Yan, B. Tochhawng, L. Jayapal, M. Koh, S. Tay, H. Maciver, S. Hooi, S. Salto-Tellez, M. Kumar, Alan Prem Goh, Y. Lim, Y. Yap, C. |
| author_sort | Zhuo, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrixdegrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/ uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. |
| first_indexed | 2025-11-14T09:02:40Z |
| format | Journal Article |
| id | curtin-20.500.11937-40322 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:02:40Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-403222017-09-13T13:37:32Z Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade Zhuo, J. Tan, E. Yan, B. Tochhawng, L. Jayapal, M. Koh, S. Tay, H. Maciver, S. Hooi, S. Salto-Tellez, M. Kumar, Alan Prem Goh, Y. Lim, Y. Yap, C. Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrixdegrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/ uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. 2012 Journal Article http://hdl.handle.net/20.500.11937/40322 10.1371/journal.pone.0043594 Public Library of Science fulltext |
| spellingShingle | Zhuo, J. Tan, E. Yan, B. Tochhawng, L. Jayapal, M. Koh, S. Tay, H. Maciver, S. Hooi, S. Salto-Tellez, M. Kumar, Alan Prem Goh, Y. Lim, Y. Yap, C. Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title | Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title_full | Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title_fullStr | Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title_full_unstemmed | Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title_short | Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| title_sort | gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade |
| url | http://hdl.handle.net/20.500.11937/40322 |