PMID- 27324860
OWN - NLM
STAT- MEDLINE
DCOM- 20180724
LR  - 20231111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jun 21
TI  - MDCK cells expressing constitutively active Yes-associated protein (YAP) undergo 
      apical extrusion depending on neighboring cell status.
PG  - 28383
LID - 10.1038/srep28383 [doi]
LID - 28383
AB  - 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.
FAU - Chiba, Takanori
AU  - Chiba T
AD  - Department of Developmental and Regenerative Biology, Medical Research Institute, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      Japan.
AD  - Department of Molecular Endocrinology and Metabolism, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, Japan.
FAU - Ishihara, Erika
AU  - Ishihara E
AD  - Department of Developmental and Regenerative Biology, Medical Research Institute, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      Japan.
FAU - Miyamura, Norio
AU  - Miyamura N
AD  - Department of Developmental and Regenerative Biology, Medical Research Institute, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      Japan.
FAU - Narumi, Rika
AU  - Narumi R
AD  - Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido 
      University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 
      7, Kita-ku, Sapporo, Hokkaido, Japan.
FAU - Kajita, Mihoko
AU  - Kajita M
AD  - Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido 
      University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 
      7, Kita-ku, Sapporo, Hokkaido, Japan.
FAU - Fujita, Yasuyuki
AU  - Fujita Y
AD  - Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido 
      University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 
      7, Kita-ku, Sapporo, Hokkaido, Japan.
FAU - Suzuki, Akira
AU  - Suzuki A
AD  - Division of Cancer Genetics, Medical Institute of Bioregulation, Kyushu 
      University, 3-1-1 Maidashi Higashi-ku, Fukuoka, Japan.
AD  - Division of Molecular and Cellular Biology, Kobe University Graduate School of 
      Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan.
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
AD  - Department of Molecular Endocrinology and Metabolism, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, Japan.
FAU - Nishina, Hiroshi
AU  - Nishina H
AD  - Department of Developmental and Regenerative Biology, Medical Research Institute, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160621
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Filamins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Vimentin)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Cell Communication
MH  - Dogs
MH  - Filamins/metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Madin Darby Canine Kidney Cells
MH  - Microscopy, Fluorescence
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Domains
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors
MH  - Vimentin/metabolism
MH  - YAP-Signaling Proteins
MH  - ras Proteins/metabolism
MH  - src-Family Kinases/metabolism
PMC - PMC4914932
EDAT- 2016/06/22 06:00
MHDA- 2018/07/25 06:00
PMCR- 2016/06/21
CRDT- 2016/06/22 06:00
PHST- 2016/01/18 00:00 [received]
PHST- 2016/06/03 00:00 [accepted]
PHST- 2016/06/22 06:00 [entrez]
PHST- 2016/06/22 06:00 [pubmed]
PHST- 2018/07/25 06:00 [medline]
PHST- 2016/06/21 00:00 [pmc-release]
AID - srep28383 [pii]
AID - 10.1038/srep28383 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jun 21;6:28383. doi: 10.1038/srep28383.