Abstract
Normal epithelial tissues often put anti‐tumorigenic pressure on newly emerged oncogenic cells through cell–cell communications. In Drosophila epithelium, clones of oncogenic cells mutant for evolutionarily conserved apico‐basal polarity genes such as scribble (scrib) and discs large (dlg) are actively eliminated when surrounded by normal cells. It has been reported that c‐Jun N‐terminal kinase (JNK) signaling in polarity‐deficient cells is crucial for their cell death. However, the mechanism by which normal epithelial tissues exert anti‐tumorigenic effects on polarity‐deficient cells had been elusive. Here, I describe our genetic studies in Drosophila epithelium especially focused on the role of surrounding normal epithelial cells in response to the emergence of polarity‐deficient cells. Furthermore, I also describe recent studies regarding the mechanism by which polarity‐deficient cells are extruded from the tissue, and discuss future perspectives on the study of cell–cell communications in epithelial homeostasis.
Highlights
Normal development and tissue homeostasis in multicellular organ‐ isms are robustly regulated through cell–cell interactions that coor‐ dinate cell proliferation and cell death
Oncogenic cells activating an oncogene such as Ras, Src, ErbB2, or YAP are eliminated from the epithelial layer when surrounded by wild‐type cells in mammals (Chiba et al, 2016; Hogan et al, 2009; Kajita et al, 2010; Leung & Brugge, 2012)
The removal of surrounding wild‐type cells by genetically inducing cell death al‐ lows these polarity‐deficient mutant cells to overgrow (Brumby & Richardson, 2003), suggesting that polarity‐deficient cells are ac‐ tively eliminated from the epithelial tissue through “competitive” interactions with surrounding wild‐type cells, a form of “cell compe‐ tition” (Claveria & Torres, 2016; Di Gregorio, Bowling, & Rodriguez, 2016; Madan, Gogna, & Moreno, 2018; Morata & Ripoll, 1975; Nagata & Igaki, 2018)
Summary
Normal development and tissue homeostasis in multicellular organ‐ isms are robustly regulated through cell–cell interactions that coor‐ dinate cell proliferation and cell death. To understand the mechanism by which normal epithelial cells exert anti‐tumor effects against oncogenic polarity‐deficient cells, we analyzed the spatial pattern of cell elimination in the Drosophila eye‐antennal imaginal epithelium bearing scrib mutant cells (Ohsawa et al, 2011).
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