Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells

Abstract Missense mutations of TP53 are extremely common, and mutant p53 accumulation and gain-of-function play crucial roles in human ovarian cancer. Here, we investigated the role of mutant p53 in cell migration and invasion as well as its underlying molecular mechanisms in human ovarian cancer ce...

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Autores principales:	Ji-Hye Ahn, Tae Jin Kim, Jae Ho Lee, Jung-Hye Choi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1653a13b3dd7420092575dd7043c22ec
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spelling	oai:doaj.org-article:1653a13b3dd7420092575dd7043c22ec2021-12-02T15:06:17ZMutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells10.1038/s41598-017-08880-42045-2322https://doaj.org/article/1653a13b3dd7420092575dd7043c22ec2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08880-4https://doaj.org/toc/2045-2322Abstract Missense mutations of TP53 are extremely common, and mutant p53 accumulation and gain-of-function play crucial roles in human ovarian cancer. Here, we investigated the role of mutant p53 in cell migration and invasion as well as its underlying molecular mechanisms in human ovarian cancer cells. Overexpression of mutant p53 significantly increased migration and invasion in p53-null SKOV3 cells. In contrast, knockdown of mutant p53 significantly compromised mutant p53-induced cell migration and invasion. Microarray analysis revealed that several migration/invasion-related genes, including S1PR1 (Sphingosine-1-phosphate receptor 1) and THBS1 (Thrombospodin 1), were significantly upregulated in SKOV3 cells that overexpressed mutant p53-R248 (SKOV3R248). We found that Rad21 is involved in the transcriptional regulation of the migration/invasion-related genes induced by mutant p53-R248. Knockdown of Rad21 significantly attenuated the mutant p53-R248-induced invasion and the expressions of S1PR1 and THBS1. Moreover, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that mutant p53 interacts with Rad21 and binds to the Rad21-binding elements in the S1PR1 and THBS1 genes. Finally, downregulation of S1PR1 significantly attenuated the invasion driven by mutant p53-R248. These novel findings reveal that mutant p53-R248 maintains gain-of-function activity to stimulate cell invasion and induces the related gene expressions through an interaction with Rad21 in human ovarian cancer cells.Ji-Hye AhnTae Jin KimJae Ho LeeJung-Hye ChoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ji-Hye Ahn Tae Jin Kim Jae Ho Lee Jung-Hye Choi Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
description	Abstract Missense mutations of TP53 are extremely common, and mutant p53 accumulation and gain-of-function play crucial roles in human ovarian cancer. Here, we investigated the role of mutant p53 in cell migration and invasion as well as its underlying molecular mechanisms in human ovarian cancer cells. Overexpression of mutant p53 significantly increased migration and invasion in p53-null SKOV3 cells. In contrast, knockdown of mutant p53 significantly compromised mutant p53-induced cell migration and invasion. Microarray analysis revealed that several migration/invasion-related genes, including S1PR1 (Sphingosine-1-phosphate receptor 1) and THBS1 (Thrombospodin 1), were significantly upregulated in SKOV3 cells that overexpressed mutant p53-R248 (SKOV3R248). We found that Rad21 is involved in the transcriptional regulation of the migration/invasion-related genes induced by mutant p53-R248. Knockdown of Rad21 significantly attenuated the mutant p53-R248-induced invasion and the expressions of S1PR1 and THBS1. Moreover, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that mutant p53 interacts with Rad21 and binds to the Rad21-binding elements in the S1PR1 and THBS1 genes. Finally, downregulation of S1PR1 significantly attenuated the invasion driven by mutant p53-R248. These novel findings reveal that mutant p53-R248 maintains gain-of-function activity to stimulate cell invasion and induces the related gene expressions through an interaction with Rad21 in human ovarian cancer cells.
format	article
author	Ji-Hye Ahn Tae Jin Kim Jae Ho Lee Jung-Hye Choi
author_facet	Ji-Hye Ahn Tae Jin Kim Jae Ho Lee Jung-Hye Choi
author_sort	Ji-Hye Ahn
title	Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
title_short	Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
title_full	Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
title_fullStr	Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
title_full_unstemmed	Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells
title_sort	mutant p53 stimulates cell invasion through an interaction with rad21 in human ovarian cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1653a13b3dd7420092575dd7043c22ec
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Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells

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