Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells

Growth factor receptor bound protein 7 (GRB7) plays an important role in regulating the growth and metastasis of ovarian cancer. Angiogenesis is the basis for the growth, invasion, and metastasis of malignant tumors. In the current study, we aimed to determine whether GRB7 plays a role in regulating...

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Autores principales: Qiong Xu, Zequn Liu, Zhi-qin Zhu, Yue Fan, Rui Chen, Xiao-hui Xie, Mi Cheng
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Lenguaje:EN
Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/69233f7bbada4f6cbf1a886102d0f0fe
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spelling oai:doaj.org-article:69233f7bbada4f6cbf1a886102d0f0fe2021-11-17T14:21:59ZKnockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells2165-59792165-598710.1080/21655979.2021.2005225https://doaj.org/article/69233f7bbada4f6cbf1a886102d0f0fe2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005225https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Growth factor receptor bound protein 7 (GRB7) plays an important role in regulating the growth and metastasis of ovarian cancer. Angiogenesis is the basis for the growth, invasion, and metastasis of malignant tumors. In the current study, we aimed to determine whether GRB7 plays a role in regulating angiogenesis in ovarian cancer. Immunohistochemistry on tissue microarray showed that GRB7 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) protein expression were positively correlated in ovarian cancer tissues. GRB7 knockdown suppressed vascular endothelial growth factor A (VEGFA) expression and reduced VEGFA secretion. The effects of GRB7-silenced SKOV-3 cells on human umbilical vein endothelial cells (HUVECs) were evaluated using a transwell cell co-culture model, which showed that knockdown of GRB7 in SKOV-3 cells suppressed HUVEC proliferation, migration, invasion, and tube formation. Moreover, knockdown of GRB7 in SKOV-3 cells downregulated the expression of proteins associated with angiogenesis, including vascular endothelial growth factor receptor-2 (VEGFR2), mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), notch receptor 1 (NOTCH1), and delta-like canonical Notch ligand 4 (DLL4) in HUVECs. In conclusion, knockdown of GRB7 in ovarian cancer cells is an attractive potential therapeutic target for the suppression of angiogenesis in ovarian cancer. GRB7 may regulate angiogenesis through VEGFA/VEGFR2 signaling and its downstream pathways.Qiong XuZequn LiuZhi-qin ZhuYue FanRui ChenXiao-hui XieMi ChengTaylor & Francis Grouparticleovarian cancergrb7angiogenesisco-culturehuvecsBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution DOAJ
collection DOAJ
language EN
topic ovarian cancer
grb7
angiogenesis
co-culture
huvecs
Biotechnology
TP248.13-248.65
spellingShingle ovarian cancer
grb7
angiogenesis
co-culture
huvecs
Biotechnology
TP248.13-248.65
Qiong Xu
Zequn Liu
Zhi-qin Zhu
Yue Fan
Rui Chen
Xiao-hui Xie
Mi Cheng
Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
description Growth factor receptor bound protein 7 (GRB7) plays an important role in regulating the growth and metastasis of ovarian cancer. Angiogenesis is the basis for the growth, invasion, and metastasis of malignant tumors. In the current study, we aimed to determine whether GRB7 plays a role in regulating angiogenesis in ovarian cancer. Immunohistochemistry on tissue microarray showed that GRB7 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) protein expression were positively correlated in ovarian cancer tissues. GRB7 knockdown suppressed vascular endothelial growth factor A (VEGFA) expression and reduced VEGFA secretion. The effects of GRB7-silenced SKOV-3 cells on human umbilical vein endothelial cells (HUVECs) were evaluated using a transwell cell co-culture model, which showed that knockdown of GRB7 in SKOV-3 cells suppressed HUVEC proliferation, migration, invasion, and tube formation. Moreover, knockdown of GRB7 in SKOV-3 cells downregulated the expression of proteins associated with angiogenesis, including vascular endothelial growth factor receptor-2 (VEGFR2), mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), notch receptor 1 (NOTCH1), and delta-like canonical Notch ligand 4 (DLL4) in HUVECs. In conclusion, knockdown of GRB7 in ovarian cancer cells is an attractive potential therapeutic target for the suppression of angiogenesis in ovarian cancer. GRB7 may regulate angiogenesis through VEGFA/VEGFR2 signaling and its downstream pathways.
format article
author Qiong Xu
Zequn Liu
Zhi-qin Zhu
Yue Fan
Rui Chen
Xiao-hui Xie
Mi Cheng
author_facet Qiong Xu
Zequn Liu
Zhi-qin Zhu
Yue Fan
Rui Chen
Xiao-hui Xie
Mi Cheng
author_sort Qiong Xu
title Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
title_short Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
title_full Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
title_fullStr Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
title_full_unstemmed Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells
title_sort knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor a in ovarian cancer cells
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/69233f7bbada4f6cbf1a886102d0f0fe
work_keys_str_mv AT qiongxu knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT zequnliu knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT zhiqinzhu knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT yuefan knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT ruichen knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT xiaohuixie knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
AT micheng knockdownofgrowthfactorreceptorboundprotein7suppressesangiogenesisbyinhibitingthesecretionofvascularendothelialgrowthfactorainovariancancercells
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