Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules.
The actin-bundling protein, fascin, is a member of the cytoskeletal protein family that has restricted expression in specialized normal cells. However, many studies have reported the induction of this protein in various transformed cells including breast cancer cells. While the role of fascin in the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3208623?pdf=render |
| _version_ | 1818290830446690304 |
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| author | Monther Al-Alwan Safiah Olabi Hazem Ghebeh Eman Barhoush Asma Tulbah Taher Al-Tweigeri Dahish Ajarim Chaker Adra |
| author_facet | Monther Al-Alwan Safiah Olabi Hazem Ghebeh Eman Barhoush Asma Tulbah Taher Al-Tweigeri Dahish Ajarim Chaker Adra |
| author_sort | Monther Al-Alwan |
| collection | DOAJ |
| description | The actin-bundling protein, fascin, is a member of the cytoskeletal protein family that has restricted expression in specialized normal cells. However, many studies have reported the induction of this protein in various transformed cells including breast cancer cells. While the role of fascin in the regulation of breast cancer cell migration has been previously shown, the underlying molecular mechanism remained poorly defined. We have used variety of immunological and functional assays to study whether fascin regulates breast cancer metastasis-associated molecules. In this report we found a direct relationship between fascin expression in breast cancer patients and; metastasis and shorter disease-free survival. Most importantly, in vitro interference with fascin expression by loss or gain of function demonstrates a central role for this protein in regulating the cell morphology, migration and invasion potential. Our results show that fascin regulation of invasion is mediated via modulating several metastasis-associated genes. We show for the first time that fascin down-regulates the expression and nuclear translocation of a key metastasis suppressor protein known as breast cancer metastasis suppressor-1 (BRMS1). In addition, fascin up-regulates NF-kappa B activity, which is essential for metastasis. Importantly, fascin up-regulates other proteins that are known to be critical for the execution of metastasis such as urokinase-type plasminogen activator (uPA) and the matrix metalloproteases (MMP)-2 and MMP-9. This study demonstrates that fascin expression in breast cancer cells establishes a gene expression profile consistent with metastatic tumors and offers a potential therapeutic intervention in metastatic breast cancer treatment through fascin targeting. |
| first_indexed | 2024-12-13T02:34:24Z |
| format | Article |
| id | doaj.art-db6063dfabfd4160b6734f1e900dc24e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T02:34:24Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-db6063dfabfd4160b6734f1e900dc24e2022-12-22T00:02:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2733910.1371/journal.pone.0027339Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules.Monther Al-AlwanSafiah OlabiHazem GhebehEman BarhoushAsma TulbahTaher Al-TweigeriDahish AjarimChaker AdraThe actin-bundling protein, fascin, is a member of the cytoskeletal protein family that has restricted expression in specialized normal cells. However, many studies have reported the induction of this protein in various transformed cells including breast cancer cells. While the role of fascin in the regulation of breast cancer cell migration has been previously shown, the underlying molecular mechanism remained poorly defined. We have used variety of immunological and functional assays to study whether fascin regulates breast cancer metastasis-associated molecules. In this report we found a direct relationship between fascin expression in breast cancer patients and; metastasis and shorter disease-free survival. Most importantly, in vitro interference with fascin expression by loss or gain of function demonstrates a central role for this protein in regulating the cell morphology, migration and invasion potential. Our results show that fascin regulation of invasion is mediated via modulating several metastasis-associated genes. We show for the first time that fascin down-regulates the expression and nuclear translocation of a key metastasis suppressor protein known as breast cancer metastasis suppressor-1 (BRMS1). In addition, fascin up-regulates NF-kappa B activity, which is essential for metastasis. Importantly, fascin up-regulates other proteins that are known to be critical for the execution of metastasis such as urokinase-type plasminogen activator (uPA) and the matrix metalloproteases (MMP)-2 and MMP-9. This study demonstrates that fascin expression in breast cancer cells establishes a gene expression profile consistent with metastatic tumors and offers a potential therapeutic intervention in metastatic breast cancer treatment through fascin targeting.http://europepmc.org/articles/PMC3208623?pdf=render |
| spellingShingle | Monther Al-Alwan Safiah Olabi Hazem Ghebeh Eman Barhoush Asma Tulbah Taher Al-Tweigeri Dahish Ajarim Chaker Adra Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS ONE |
| title | Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. |
| title_full | Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. |
| title_fullStr | Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. |
| title_full_unstemmed | Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. |
| title_short | Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. |
| title_sort | fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis associated molecules |
| url | http://europepmc.org/articles/PMC3208623?pdf=render |
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