RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells
Angiogenesis is a hallmark of cancer cell malignancy. The role of the RHO family GTPase RHOG in angiogenesis in vascular endothelial cells has recently been elucidated. However, the regulation of RHOG during this process, as well as its cross-talk with other RHO GTPases, have yet to be fully examine...
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2019
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| Online Access: | http://hdl.handle.net/10725/11396 https://doi.org/10.3390/cells8020171 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2073-4409/8/2/171 |
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| _version_ | 1864513488713416704 |
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| author | El Atat, Oula |
| author2 | Fakih, Amira El-Sibai, Mirvat |
| author2_role | author author |
| author_facet | El Atat, Oula Fakih, Amira El-Sibai, Mirvat |
| author_role | author |
| dc.creator.none.fl_str_mv | El Atat, Oula Fakih, Amira El-Sibai, Mirvat |
| dc.date.none.fl_str_mv | 2019-10-08T12:26:39Z 2019-10-08T12:26:39Z 2019 2019-10-08 |
| dc.identifier.none.fl_str_mv | 2073-4409 http://hdl.handle.net/10725/11396 https://doi.org/10.3390/cells8020171 El Atat, O., Fakih, A., & El-Sibai, M. (2019). RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial Cells. Cells, 8(2), 171. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2073-4409/8/2/171 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Cells |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Angiogenesis is a hallmark of cancer cell malignancy. The role of the RHO family GTPase RHOG in angiogenesis in vascular endothelial cells has recently been elucidated. However, the regulation of RHOG during this process, as well as its cross-talk with other RHO GTPases, have yet to be fully examined. In this study, we found that siRNA-mediated depletion of RHOG strongly inhibits tube formation in vascular endothelial cells (ECV cells), an effect reversed by transfecting dominant active constructs of CDC42 or RAC1 in the RHOG-depleted cells. We also found CDC42 to be upstream from RAC1 in these cells. Inhibiting either Phosphatidyl inositol (3) kinase (PI3K) with Wortmannin or the mitogen-activated protein kinase extracellular-regulated kinase (MAPK ERK) with U0126 leads to the inhibition of tube formation. While knocking down either RHO, GTPase did not affect p-AKT levels, and p-ERK decreased in response to the knocking down of RHOG, CDC42 or RAC1. Recovering active RHO GTPases in U0126-treated cells also did not reverse the inhibition of tube formation, placing ERK downstream from PI3K-RHOG-CDC42-RAC1 in vascular endothelial cells. Finally, RHOA and the Rho activated protein kinases ROCK1 and ROCK2 positively regulated tube formation independently of ERK, while RHOC seemed to inhibit the process. Collectively, our data confirmed the essential role of RHOG in angiogenesis, shedding light on a potential new therapeutic target for cancer malignancy and metastasis |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_d218a1d609d162c40c1ff1db059595ad |
| identifier_str_mv | 2073-4409 El Atat, O., Fakih, A., & El-Sibai, M. (2019). RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial Cells. Cells, 8(2), 171. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/11396 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cellsEl Atat, OulaFakih, AmiraEl-Sibai, MirvatAngiogenesis is a hallmark of cancer cell malignancy. The role of the RHO family GTPase RHOG in angiogenesis in vascular endothelial cells has recently been elucidated. However, the regulation of RHOG during this process, as well as its cross-talk with other RHO GTPases, have yet to be fully examined. In this study, we found that siRNA-mediated depletion of RHOG strongly inhibits tube formation in vascular endothelial cells (ECV cells), an effect reversed by transfecting dominant active constructs of CDC42 or RAC1 in the RHOG-depleted cells. We also found CDC42 to be upstream from RAC1 in these cells. Inhibiting either Phosphatidyl inositol (3) kinase (PI3K) with Wortmannin or the mitogen-activated protein kinase extracellular-regulated kinase (MAPK ERK) with U0126 leads to the inhibition of tube formation. While knocking down either RHO, GTPase did not affect p-AKT levels, and p-ERK decreased in response to the knocking down of RHOG, CDC42 or RAC1. Recovering active RHO GTPases in U0126-treated cells also did not reverse the inhibition of tube formation, placing ERK downstream from PI3K-RHOG-CDC42-RAC1 in vascular endothelial cells. Finally, RHOA and the Rho activated protein kinases ROCK1 and ROCK2 positively regulated tube formation independently of ERK, while RHOC seemed to inhibit the process. Collectively, our data confirmed the essential role of RHOG in angiogenesis, shedding light on a potential new therapeutic target for cancer malignancy and metastasisPublishedN/A2019-10-08T12:26:39Z2019-10-08T12:26:39Z20192019-10-08Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2073-4409http://hdl.handle.net/10725/11396https://doi.org/10.3390/cells8020171El Atat, O., Fakih, A., & El-Sibai, M. (2019). RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial Cells. Cells, 8(2), 171.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.mdpi.com/2073-4409/8/2/171enCellsinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/113962021-03-19T10:47:37Z |
| spellingShingle | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells El Atat, Oula |
| status_str | publishedVersion |
| title | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| title_full | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| title_fullStr | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| title_full_unstemmed | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| title_short | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| title_sort | RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells |
| url | http://hdl.handle.net/10725/11396 https://doi.org/10.3390/cells8020171 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2073-4409/8/2/171 |