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Cell competition: Emerging mechanisms to eliminate neighbors
1Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Abstract:
Cell competition is a context-dependent cell elimination through short-range cell-cell interaction, in which cells with higher fitness eliminate neighboring less-fit or oncogenic cells within the growing tissue. Cell competition can be triggered by many different factors such as heterozygous mutations in the ribosomal protein genes (which are called "Minute" mutations), elevated Myc, Yorkie/YAP, Wg/Wnt, JAK-STAT, Ras, or Src activity, and loss of Mahjong/VprBP, endocytic pathway components, or apicobasal cell polarity. Studies on the mechanisms and roles of cell competition have suggested that cell competition can be divided into two types: selection of fitter cells or elimination of oncogenic cells. The former type of cell competition includes Minute or Myc-induced cell competition that is considered to be dependent on the relative level of protein synthesis. The later type of cell competition includes tumor-suppressive cell competition triggered by loss of cell polarity genes such as scribble (scrib) or discs large (dlg). Genetic studies in Drosophila during the past decade have provided significant progress in understanding the mechanisms of these phenomena. At the same time, these studies have now raised new questions; how do different mechanisms contribute or cooperate to drive cell competition, do common mechanisms exist in different types of cell competition, and what are the physiological roles of these cell competition phenomena?
Insights
Cell competition eliminates unfit cells in developing tissues. This process, studied in Drosophila, involves mechanisms like ribosomal protein mutations and cell polarity loss, raising questions about its diverse roles.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cell competition is a mechanism where fitter cells eliminate less-fit or oncogenic neighbors within developing tissues.
- It can be triggered by various genetic and pathway alterations, including ribosomal protein gene mutations ('Minute' mutations) and oncogenic signaling pathways (Myc, Ras, Src).
- Two main types are recognized: selection of fitter cells (e.g., Minute or Myc-induced) and elimination of oncogenic cells (e.g., due to loss of cell polarity).
Purpose of the Study:
- To review and synthesize current understanding of cell competition mechanisms and roles.
- To highlight the progress made through genetic studies in Drosophila.
- To identify outstanding questions regarding the cooperation of different mechanisms and the physiological significance of cell competition.
Main Methods:
- Genetic studies in Drosophila models.
- Analysis of cell-cell interactions and fitness differences.
- Investigation of signaling pathways (Myc, Wnt, JAK-STAT, Ras, Src) and cellular processes (protein synthesis, cell polarity, endocytosis).
Main Results:
- Cell competition is a context-dependent process involving short-range cell-cell interactions.
- Different triggers lead to distinct types of cell competition, influencing tissue development and potentially tumor suppression.
- Drosophila research has significantly advanced the understanding of these phenomena.
Conclusions:
- Cell competition plays crucial roles in tissue homeostasis and development.
- Further research is needed to elucidate how diverse mechanisms contribute to and cooperate in cell competition.
- Understanding the physiological roles of cell competition is essential for comprehending tissue development and disease prevention.
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