MDCK cells expressing constitutively active Yes-associated protein (YAP) undergo apical extrusion depending on neighboring cell status

Sci Rep. 2016 Jun 21:6:28383. doi: 10.1038/srep28383.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Communication
  • Dogs
  • Filamins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Madin Darby Canine Kidney Cells
  • Microscopy, Fluorescence
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Domains
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Vimentin / metabolism
  • YAP-Signaling Proteins
  • ras Proteins / metabolism
  • src-Family Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Filamins
  • Phosphoproteins
  • Trans-Activators
  • Transcription Factors
  • Vimentin
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • src-Family Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ras Proteins