CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer

C-terminal tensin-like (CTEN) belongs to the tensin gene family, which encodes proteins that localize to focal adhesions and modulate integrin function. Accumulating studies have reported that CTEN expression can be upregulated or downregulated in different types of cancers, suggesting that CTEN has...

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Autores principales:	Xiangdong Lu PhD, Bin Zhou PhD, Minmin Cao PhD, Qin Shao PhD, Yukai Pan PhD, Tao Zhao PhD
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/283c07745f264f539adc31f8eb5c4472
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spelling	oai:doaj.org-article:283c07745f264f539adc31f8eb5c44722021-12-02T01:04:23ZCTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer1533-033810.1177/15330338211045506https://doaj.org/article/283c07745f264f539adc31f8eb5c44722021-11-01T00:00:00Zhttps://doi.org/10.1177/15330338211045506https://doaj.org/toc/1533-0338C-terminal tensin-like (CTEN) belongs to the tensin gene family, which encodes proteins that localize to focal adhesions and modulate integrin function. Accumulating studies have reported that CTEN expression can be upregulated or downregulated in different types of cancers, suggesting that CTEN has both oncogenic and tumor suppressor functions. In this study, by analyzing the expression level of CTEN in the human breast cancer (BRCA) samples from the clinically annotated genomic database, The Cancer Genome Atlas, we found that CTEN was downregulated in different BRCA subclasses, including luminal, human epidermal growth factor receptor 2 positive and triple-negative BRCA. Consistently, the protein level of CTEN was also reduced in BRCA based on the Proteomic Tumor Analysis Consortium. In contrast, vascular endothelial growth factor A (VEGFA), a signal protein that stimulates the formation of blood vessels, was upregulated in BRCA. CTEN overexpression in human umbilical vein endothelial cells and MCF7 significantly suppressed the expression of VEGFA, inhibited cell proliferation, migration, and tube formation in vitro. Mechanistically, CTEN bind to casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin-protein ligase, and decreased the β-catenin expression. In turn, the downregulation of β-catenin reduced the expression of VEGFA. Rescuing β-catenin expression effectively ameliorated the effect of CTEN overexpression in cell proliferation, migration, and tube formation. In conclusion, CTEN inhibited tumor angiogenesis by targeting VEGFA through c-Cbl-mediated down-regulation of β-catenin and may serve as a tumor suppressor in BRCA.Xiangdong Lu PhDBin Zhou PhDMinmin Cao PhDQin Shao PhDYukai Pan PhDTao Zhao PhDSAGE PublishingarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTechnology in Cancer Research & Treatment, Vol 20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiangdong Lu PhD Bin Zhou PhD Minmin Cao PhD Qin Shao PhD Yukai Pan PhD Tao Zhao PhD CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
description	C-terminal tensin-like (CTEN) belongs to the tensin gene family, which encodes proteins that localize to focal adhesions and modulate integrin function. Accumulating studies have reported that CTEN expression can be upregulated or downregulated in different types of cancers, suggesting that CTEN has both oncogenic and tumor suppressor functions. In this study, by analyzing the expression level of CTEN in the human breast cancer (BRCA) samples from the clinically annotated genomic database, The Cancer Genome Atlas, we found that CTEN was downregulated in different BRCA subclasses, including luminal, human epidermal growth factor receptor 2 positive and triple-negative BRCA. Consistently, the protein level of CTEN was also reduced in BRCA based on the Proteomic Tumor Analysis Consortium. In contrast, vascular endothelial growth factor A (VEGFA), a signal protein that stimulates the formation of blood vessels, was upregulated in BRCA. CTEN overexpression in human umbilical vein endothelial cells and MCF7 significantly suppressed the expression of VEGFA, inhibited cell proliferation, migration, and tube formation in vitro. Mechanistically, CTEN bind to casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin-protein ligase, and decreased the β-catenin expression. In turn, the downregulation of β-catenin reduced the expression of VEGFA. Rescuing β-catenin expression effectively ameliorated the effect of CTEN overexpression in cell proliferation, migration, and tube formation. In conclusion, CTEN inhibited tumor angiogenesis by targeting VEGFA through c-Cbl-mediated down-regulation of β-catenin and may serve as a tumor suppressor in BRCA.
format	article
author	Xiangdong Lu PhD Bin Zhou PhD Minmin Cao PhD Qin Shao PhD Yukai Pan PhD Tao Zhao PhD
author_facet	Xiangdong Lu PhD Bin Zhou PhD Minmin Cao PhD Qin Shao PhD Yukai Pan PhD Tao Zhao PhD
author_sort	Xiangdong Lu PhD
title	CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
title_short	CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
title_full	CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
title_fullStr	CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
title_full_unstemmed	CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer
title_sort	cten inhibits tumor angiogenesis and growth by targeting vegfa through down-regulation of β-catenin in breast cancer
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/283c07745f264f539adc31f8eb5c4472
work_keys_str_mv	AT xiangdongluphd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer AT binzhouphd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer AT minmincaophd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer AT qinshaophd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer AT yukaipanphd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer AT taozhaophd cteninhibitstumorangiogenesisandgrowthbytargetingvegfathroughdownregulationofbcatenininbreastcancer
_version_	1718403305401483264

CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer

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