Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
Scientific Reports Volume 7
Page 5408-
published_at 2017-07-14
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Title ( eng ) |
Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling
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Creator |
Taniguchi Yuri
Yamawaki Yosuke
Gao Jing
Takeuchi Hiroshi
Hirata Masato
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Source Title |
Scientific Reports
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Volume | 7 |
Start Page | 5408 |
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.
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Descriptions |
This work was supported by grants from JSPS KAKENHI Grant Numbers JP15K20372, JP17K11644, JP16K11503.
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Language |
eng
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Resource Type | journal article |
Publisher |
Nature Research
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Date of Issued | 2017-07-14 |
Rights |
© The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Publish Type | Version of Record |
Access Rights | open access |
Source Identifier |
[ISSN] 2045-2322
[DOI] 10.1038/s41598-017-05908-7
[DOI] https://doi.org/10.1038/s41598-017-05908-7
[PMID] 28710365
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