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A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)

At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring tr...

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Autores principales: Yamamoto, Sayaka, Yako, Yuta, Fujioka, Yoichiro, Kajita, Mihoko, Kameyama, Takeshi, Kon, Shunsuke, Ishikawa, Susumu, Ohba, Yusuke, Ohno, Yusuke, Kihara, Akio, Fujita, Yasuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751600/
https://www.ncbi.nlm.nih.gov/pubmed/26631556
http://dx.doi.org/10.1091/mbc.E15-03-0161
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author Yamamoto, Sayaka
Yako, Yuta
Fujioka, Yoichiro
Kajita, Mihoko
Kameyama, Takeshi
Kon, Shunsuke
Ishikawa, Susumu
Ohba, Yusuke
Ohno, Yusuke
Kihara, Akio
Fujita, Yasuyuki
author_facet Yamamoto, Sayaka
Yako, Yuta
Fujioka, Yoichiro
Kajita, Mihoko
Kameyama, Takeshi
Kon, Shunsuke
Ishikawa, Susumu
Ohba, Yusuke
Ohno, Yusuke
Kihara, Akio
Fujita, Yasuyuki
author_sort Yamamoto, Sayaka
collection PubMed
description At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)–S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.
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spelling pubmed-47516002016-04-16 A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC) Yamamoto, Sayaka Yako, Yuta Fujioka, Yoichiro Kajita, Mihoko Kameyama, Takeshi Kon, Shunsuke Ishikawa, Susumu Ohba, Yusuke Ohno, Yusuke Kihara, Akio Fujita, Yasuyuki Mol Biol Cell Articles At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)–S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. The American Society for Cell Biology 2016-02-01 /pmc/articles/PMC4751600/ /pubmed/26631556 http://dx.doi.org/10.1091/mbc.E15-03-0161 Text en © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Yamamoto, Sayaka
Yako, Yuta
Fujioka, Yoichiro
Kajita, Mihoko
Kameyama, Takeshi
Kon, Shunsuke
Ishikawa, Susumu
Ohba, Yusuke
Ohno, Yusuke
Kihara, Akio
Fujita, Yasuyuki
A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title_full A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title_fullStr A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title_full_unstemmed A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title_short A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)
title_sort role of the sphingosine-1-phosphate (s1p)–s1p receptor 2 pathway in epithelial defense against cancer (edac)
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751600/
https://www.ncbi.nlm.nih.gov/pubmed/26631556
http://dx.doi.org/10.1091/mbc.E15-03-0161
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