Title: | A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC) |
Authors: | Yamamoto, Sayaka Browse this author |
Yako, Yuta Browse this author |
Fujioka, Yoichiro Browse this author |
Kajita, Mihoko Browse this author →KAKEN DB |
Kameyama, Takeshi Browse this author →KAKEN DB |
Kon, Shunsuke Browse this author →KAKEN DB |
Ishikawa, Susumu Browse this author |
Ohba, Yusuke Browse this author →KAKEN DB |
Ohno, Yusuke Browse this author →KAKEN DB |
Kihara, Akio Browse this author →KAKEN DB |
Fujita, Yasuyuki Browse this author →KAKEN DB |
Issue Date: | 1-Feb-2016 |
Publisher: | American Society for Cell Biology |
Journal Title: | Molecular biology of the cell |
Volume: | 27 |
Issue: | 3 |
Start Page: | 491 |
End Page: | 499 |
Publisher DOI: | 10.1091/mbc.E15-03-0161 |
Abstract: | 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. |
Rights: | http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/61130 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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