Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling

Abstract The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Satoshi Asano, Yuri Taniguchi, Yosuke Yamawaki, Jing Gao, Kae Harada, Hiroshi Takeuchi, Masato Hirata, Takashi Kanematsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c36f2485236423fb4c049aefc12bb3c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1c36f2485236423fb4c049aefc12bb3c
record_format	dspace
spelling	oai:doaj.org-article:1c36f2485236423fb4c049aefc12bb3c2021-12-02T16:06:21ZSuppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling10.1038/s41598-017-05908-72045-2322https://doaj.org/article/1c36f2485236423fb4c049aefc12bb3c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05908-7https://doaj.org/toc/2045-2322Abstract The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. Overexpression of the PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in MCF-7 cells caused significant suppression of cell migration. Consistent with these results, in comparison with wild-type cells, Prip-deficient mouse embryonic fibroblasts exhibited increased cell migration, and this was significantly attenuated upon transfection with a siRNA targeting p110α, a catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. PI3K binding to PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro, and thus the activity of PI3K was downregulated. Collectively, PRIP regulates the production of PI(3,4,5)P3 from PI(4,5)P2 by PI3K, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.Satoshi AsanoYuri TaniguchiYosuke YamawakiJing GaoKae HaradaHiroshi TakeuchiMasato HirataTakashi KanematsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satoshi Asano Yuri Taniguchi Yosuke Yamawaki Jing Gao Kae Harada Hiroshi Takeuchi Masato Hirata Takashi Kanematsu Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
description	Abstract The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. Overexpression of the PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in MCF-7 cells caused significant suppression of cell migration. Consistent with these results, in comparison with wild-type cells, Prip-deficient mouse embryonic fibroblasts exhibited increased cell migration, and this was significantly attenuated upon transfection with a siRNA targeting p110α, a catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. PI3K binding to PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro, and thus the activity of PI3K was downregulated. Collectively, PRIP regulates the production of PI(3,4,5)P3 from PI(4,5)P2 by PI3K, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.
format	article
author	Satoshi Asano Yuri Taniguchi Yosuke Yamawaki Jing Gao Kae Harada Hiroshi Takeuchi Masato Hirata Takashi Kanematsu
author_facet	Satoshi Asano Yuri Taniguchi Yosuke Yamawaki Jing Gao Kae Harada Hiroshi Takeuchi Masato Hirata Takashi Kanematsu
author_sort	Satoshi Asano
title	Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
title_short	Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
title_full	Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
title_fullStr	Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
title_full_unstemmed	Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
title_sort	suppression of cell migration by phospholipase c-related catalytically inactive protein-dependent modulation of pi3k signalling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1c36f2485236423fb4c049aefc12bb3c
work_keys_str_mv	AT satoshiasano suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT yuritaniguchi suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT yosukeyamawaki suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT jinggao suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT kaeharada suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT hiroshitakeuchi suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT masatohirata suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling AT takashikanematsu suppressionofcellmigrationbyphospholipasecrelatedcatalyticallyinactiveproteindependentmodulationofpi3ksignalling
_version_	1718385009240309760

Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling

Ejemplares similares