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Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling.
Sci Rep 2017; 7(1):5408SR

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.

Authors+Show Affiliations

Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu, 803-8580, Japan.Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan. Fukuoka Dental College, Fukuoka, 814-0193, Japan.Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan. tkanema2@hiroshima-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28710365

Citation

Asano, Satoshi, et al. "Suppression of Cell Migration By Phospholipase C-related Catalytically Inactive Protein-dependent Modulation of PI3K Signalling." Scientific Reports, vol. 7, no. 1, 2017, p. 5408.
Asano S, Taniguchi Y, Yamawaki Y, et al. Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling. Sci Rep. 2017;7(1):5408.
Asano, S., Taniguchi, Y., Yamawaki, Y., Gao, J., Harada, K., Takeuchi, H., ... Kanematsu, T. (2017). Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling. Scientific Reports, 7(1), p. 5408. doi:10.1038/s41598-017-05908-7.
Asano S, et al. Suppression of Cell Migration By Phospholipase C-related Catalytically Inactive Protein-dependent Modulation of PI3K Signalling. Sci Rep. 2017 07 14;7(1):5408. PubMed PMID: 28710365.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/07/14/ PY - 2017/04/04/received PY - 2017/06/05/accepted PY - 2017/7/16/entrez PY - 2017/7/16/pubmed PY - 2019/1/29/medline SP - 5408 EP - 5408 JF - Scientific reports JO - Sci Rep VL - 7 IS - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28710365/Suppression_of_cell_migration_by_phospholipase_C_related_catalytically_inactive_protein_dependent_modulation_of_PI3K_signalling_ L2 - http://dx.doi.org/10.1038/s41598-017-05908-7 DB - PRIME DP - Unbound Medicine ER -