Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer

Abstract Cyclooxygenase-2 (COX-2) was stated to be overexpression in various human malignancies associating with angiogenesis, metastasis and chemoresistence. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease displaying many of these characteristics. A common abnormality of PDAC is overexp...

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Autores principales:	Hai Hu, Ting Han, Meng Zhuo, Lei-lei Wu, Cuncun Yuan, Lixia Wu, Wang Lei, Feng Jiao, Li-Wei Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc85f669157f4c0ebadc90a738425622
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spelling	oai:doaj.org-article:dc85f669157f4c0ebadc90a7384256222021-12-02T11:40:52ZElevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer10.1038/s41598-017-00288-42045-2322https://doaj.org/article/dc85f669157f4c0ebadc90a7384256222017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00288-4https://doaj.org/toc/2045-2322Abstract Cyclooxygenase-2 (COX-2) was stated to be overexpression in various human malignancies associating with angiogenesis, metastasis and chemoresistence. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease displaying many of these characteristics. A common abnormality of PDAC is overexpression of specificity protein-1 (Sp1), which was said to correlate with malignant phenotypes of human cancers. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we found that Sp1 expression was positively correlated with that of COX-2 in PDAC, and that the inhibition or overexpression of Sp1 in PDAC cells leads to decreased or elevated COX-2 expression. Luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that elevated transcription of COX-2 requires Sp1 binding to sequence positions around −245/−240 of COX-2 promoter. Activated epidermal growth factor receptor (EGFR) and downstream p38 mitogen-activated protein kinase (p38-MAPK) were also profoundly altered in PDAC. The inhibition of EGFR/p38-MAPK signaling resulted in reduced Sp1 activation, decreased COX-2 and vascular endothelial growth factor (VEGF) expression. Thus, Sp1 could transcriptionally activate COX-2 expression in a process relies on activated EGFR/p38-MAPK signaling. Finally, we found that the inhibition of COX-2 leads to decreased angiogenesis in a process dependent on VEGF, which link COX-2 to angiogenesis in PDAC.Hai HuTing HanMeng ZhuoLei-lei WuCuncun YuanLixia WuWang LeiFeng JiaoLi-Wei WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hai Hu Ting Han Meng Zhuo Lei-lei Wu Cuncun Yuan Lixia Wu Wang Lei Feng Jiao Li-Wei Wang Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
description	Abstract Cyclooxygenase-2 (COX-2) was stated to be overexpression in various human malignancies associating with angiogenesis, metastasis and chemoresistence. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease displaying many of these characteristics. A common abnormality of PDAC is overexpression of specificity protein-1 (Sp1), which was said to correlate with malignant phenotypes of human cancers. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we found that Sp1 expression was positively correlated with that of COX-2 in PDAC, and that the inhibition or overexpression of Sp1 in PDAC cells leads to decreased or elevated COX-2 expression. Luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that elevated transcription of COX-2 requires Sp1 binding to sequence positions around −245/−240 of COX-2 promoter. Activated epidermal growth factor receptor (EGFR) and downstream p38 mitogen-activated protein kinase (p38-MAPK) were also profoundly altered in PDAC. The inhibition of EGFR/p38-MAPK signaling resulted in reduced Sp1 activation, decreased COX-2 and vascular endothelial growth factor (VEGF) expression. Thus, Sp1 could transcriptionally activate COX-2 expression in a process relies on activated EGFR/p38-MAPK signaling. Finally, we found that the inhibition of COX-2 leads to decreased angiogenesis in a process dependent on VEGF, which link COX-2 to angiogenesis in PDAC.
format	article
author	Hai Hu Ting Han Meng Zhuo Lei-lei Wu Cuncun Yuan Lixia Wu Wang Lei Feng Jiao Li-Wei Wang
author_facet	Hai Hu Ting Han Meng Zhuo Lei-lei Wu Cuncun Yuan Lixia Wu Wang Lei Feng Jiao Li-Wei Wang
author_sort	Hai Hu
title	Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
title_short	Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
title_full	Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
title_fullStr	Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
title_full_unstemmed	Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer
title_sort	elevated cox-2 expression promotes angiogenesis through egfr/p38-mapk/sp1-dependent signalling in pancreatic cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dc85f669157f4c0ebadc90a738425622
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Elevated COX-2 Expression Promotes Angiogenesis Through EGFR/p38-MAPK/Sp1-Dependent Signalling in Pancreatic Cancer

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