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

Satoshi Asano, Yuri Taniguchi, Yosuke Yamawaki, Jing Gao, Kae Harada, Hiroshi Takeuchi, Masato Hirata, Takashi Kanematsu

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article number5408
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

3-Phosphoinositide-Dependent Protein Kinases
Type C Phospholipases
Cell Movement
1-Phosphatidylinositol 4-Kinase
Proteins
Neoplasms
MCF-7 Cells
Phosphatidylinositols
Small Interfering RNA
Transfection
Catalytic Domain
Carrier Proteins
Down-Regulation
Fibroblasts
Breast Neoplasms
Neoplasm Metastasis
phosphoinositide-3,4,5-triphosphate

All Science Journal Classification (ASJC) codes

  • General

Cite this

Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling. / Asano, Satoshi; Taniguchi, Yuri; Yamawaki, Yosuke; Gao, Jing; Harada, Kae; Takeuchi, Hiroshi; Hirata, Masato; Kanematsu, Takashi.

In: Scientific reports, Vol. 7, No. 1, 5408, 01.12.2017.

Research output: Contribution to journalArticle

Asano, Satoshi ; Taniguchi, Yuri ; Yamawaki, Yosuke ; Gao, Jing ; Harada, Kae ; Takeuchi, Hiroshi ; Hirata, Masato ; Kanematsu, Takashi. / Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling. In: Scientific reports. 2017 ; Vol. 7, No. 1.
@article{5698e692c34547339c5027a68f4d51f8,
title = "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 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.",
author = "Satoshi Asano and Yuri Taniguchi and Yosuke Yamawaki and Jing Gao and Kae Harada and Hiroshi Takeuchi and Masato Hirata and Takashi Kanematsu",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-05908-7",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling

AU - Asano, Satoshi

AU - Taniguchi, Yuri

AU - Yamawaki, Yosuke

AU - Gao, Jing

AU - Harada, Kae

AU - Takeuchi, Hiroshi

AU - Hirata, Masato

AU - Kanematsu, Takashi

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85024390240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024390240&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-05908-7

DO - 10.1038/s41598-017-05908-7

M3 - Article

C2 - 28710365

AN - SCOPUS:85024390240

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 5408

ER -