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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MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/171 |
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| author | Oula El Atat Amira Fakih Mirvat El-Sibai |
| author_facet | Oula El Atat Amira Fakih Mirvat El-Sibai |
| author_sort | Oula El Atat |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T19:42:27Z |
| format | Article |
| id | doaj.art-8fc85de4d8d0450795c3926fb1a2b660 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:42:27Z |
| publishDate | 2019-02-01 |
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| series | Cells |
| spelling | doaj.art-8fc85de4d8d0450795c3926fb1a2b6602023-08-02T03:46:58ZengMDPI AGCells2073-44092019-02-018217110.3390/cells8020171cells8020171RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial CellsOula El Atat0Amira Fakih1Mirvat El-Sibai2Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, LebanonDepartment of Natural Sciences, Lebanese American University, Beirut 1102 2801, LebanonDepartment of Natural Sciences, Lebanese American University, Beirut 1102 2801, LebanonAngiogenesis 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.https://www.mdpi.com/2073-4409/8/2/171RHOGRAC1CDC42RHO GTPasesangiogenesisvascular endothelial cells |
| spellingShingle | Oula El Atat Amira Fakih Mirvat El-Sibai RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial Cells Cells RHOG RAC1 CDC42 RHO GTPases angiogenesis vascular endothelial cells |
| 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 |
| topic | RHOG RAC1 CDC42 RHO GTPases angiogenesis vascular endothelial cells |
| url | https://www.mdpi.com/2073-4409/8/2/171 |
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