Open AccessMDCK cells expressing constitutively active Yes-associated protein (YAP) undergo apical extrusion depending on neighboring cell status
Author(s) -
Takanori Chiba,
Erika Ishihara,
Norio Miyamura,
Rika Narumi,
Mihoko Kajita,
Yasuyuki Fujita,
Akira Suzuki,
Yoshihiro Ogawa,
Hiroshi Nishina
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28383
Subject(s) - microbiology and biotechnology , filamin , cell , biology , vimentin , pi3k/akt/mtor pathway , protein kinase a , cell growth , kinase , signal transduction , cytoskeleton , genetics , immunology , immunohistochemistry
Cell competition is a cell-cell interaction by which a cell compares its fitness to that of neighboring cells. The cell with the relatively lower fitness level is the “loser” and actively eliminated, while the cell with the relatively higher fitness level is the “winner” and survives. Recent studies have shown that cells with high Yes-associated protein (YAP) activity win cell competitions but the mechanism is unknown. Here, we report the unexpected finding that cells overexpressing constitutively active YAP undergo apical extrusion and are losers, rather than winners, in competitions with normal mammalian epithelial cells. Inhibitors of metabolism-related proteins such as phosphoinositide-3-kinase (PI3K), mammalian target of rapamycin (mTOR), or p70S6 kinase (p70S6K) suppressed this apical extrusion, as did knockdown of vimentin or filamin in neighboring cells. Interestingly, YAP-overexpressing cells switched from losers to winners when co-cultured with cells expressing K-Ras (G12V) or v-Src. Thus, the role of YAP in deciding cell competitions depends on metabolic factors and the status of neighboring cells.