Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion
Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein...
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| Format: | article |
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2016
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| Online Access: | http://hdl.handle.net/10725/4940 http://dx.doi.org/10.3892/ijo.2016.3431 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.spandidos-publications.com/ijo/48/5/1913?text=fulltext |
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| _version_ | 1864513464926470144 |
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| author | Al-Dimassi, Saleh |
| author2 | Salloum, Gilbert Saykali, Bechara Khoury, Oula Liu, Shihui Leppla, Stephen H. Abi-Habib, Ralph El-Sibai, Mirvat |
| author2_role | author author author author author author author |
| author_facet | Al-Dimassi, Saleh Salloum, Gilbert Saykali, Bechara Khoury, Oula Liu, Shihui Leppla, Stephen H. Abi-Habib, Ralph El-Sibai, Mirvat |
| author_role | author |
| dc.creator.none.fl_str_mv | Al-Dimassi, Saleh Salloum, Gilbert Saykali, Bechara Khoury, Oula Liu, Shihui Leppla, Stephen H. Abi-Habib, Ralph El-Sibai, Mirvat |
| dc.date.none.fl_str_mv | 2016-12-14T08:43:28Z 2016-12-14T08:43:28Z 2016 2016-12-14 |
| dc.identifier.none.fl_str_mv | 1019-6439 http://hdl.handle.net/10725/4940 http://dx.doi.org/10.3892/ijo.2016.3431 Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S. H., ... & El-Sibai, M. (2016). Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. International journal of oncology, 48(5), 1913-1920. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.spandidos-publications.com/ijo/48/5/1913?text=fulltext |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | International Journal of Oncology |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_87704dc159754a0b94f792d3480e3112 |
| identifier_str_mv | 1019-6439 Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S. H., ... & El-Sibai, M. (2016). Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. International journal of oncology, 48(5), 1913-1920. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/4940 |
| publishDate | 2016 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasionAl-Dimassi, SalehSalloum, GilbertSaykali, BecharaKhoury, OulaLiu, ShihuiLeppla, Stephen H.Abi-Habib, RalphEl-Sibai, MirvatMalignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor.PublishedN/A2016-12-14T08:43:28Z2016-12-14T08:43:28Z20162016-12-14Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1019-6439http://hdl.handle.net/10725/4940http://dx.doi.org/10.3892/ijo.2016.3431Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S. H., ... & El-Sibai, M. (2016). Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. International journal of oncology, 48(5), 1913-1920.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.spandidos-publications.com/ijo/48/5/1913?text=fulltextenInternational Journal of Oncologyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/49402022-08-02T09:59:04Z |
| spellingShingle | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion Al-Dimassi, Saleh |
| status_str | publishedVersion |
| title | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| title_full | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| title_fullStr | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| title_full_unstemmed | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| title_short | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| title_sort | Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion |
| url | http://hdl.handle.net/10725/4940 http://dx.doi.org/10.3892/ijo.2016.3431 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.spandidos-publications.com/ijo/48/5/1913?text=fulltext |