Supercompetitor Status of Drosophila Myc Cells Requires p53 as a Fitness Sensor to Reprogram Metabolism and Promote Viability
Supercompetitor Status of Drosophila Myc Cells Requires p53 as a Fitness Sensor to Reprogram Metabolism and Promote Viability
In growing tissues, cell fitness disparities can provoke interactions that promote stronger cells at the expense of the weaker in a process called cell competition. The mechanistic definition of cell fitness is not understood, nor is it understood how fitness differences are recognized. Drosophila cells with extra Myc activity acquire "supercompetitor" status upon confrontation with wild-type (WT) cells, prompting the latter's elimination via apoptosis. Here we show that such confrontation enhances glycolytic flux in Myc cells and promotes their fitness and proliferation in a p53-dependent manner. Whereas p53 loss in noncompeting Myc cells is inconsequential, its loss impairs metabolism, reduces viability, and prevents the killing activity of Myc supercompetitor cells. We propose that p53 acts as a general sensor of competitive confrontation to enhance the fitness of the "winner" population. Our findings suggest that the initial confrontation between precancerous and WT cells could enhance cancer cell fitness and promote tumor progression.
- Waseda University Japan
- Columbia University Medical Center United States
- Alma Mater Studiorum University of Bologna Italy
- University of Trento Italy
Physiology, Animals; Cell Proliferation; Cells, Cultured; Coculture Techniques; Drosophila; Drosophila Proteins; Genomic Instability; Glycolysis; Oxidative Phosphorylation; Proto-Oncogene Proteins c-myc; RNA, Messenger; Tumor Suppressor Protein p53; Physiology; Molecular Biology; Cell Biology, Cell Biology, Coculture Techniques, Genomic Instability, Oxidative Phosphorylation, Proto-Oncogene Proteins c-myc, Animals, Drosophila Proteins, Drosophila, RNA, Messenger, Tumor Suppressor Protein p53, Molecular Biology, Glycolysis, Cells, Cultured, Cell Proliferation
Physiology, Animals; Cell Proliferation; Cells, Cultured; Coculture Techniques; Drosophila; Drosophila Proteins; Genomic Instability; Glycolysis; Oxidative Phosphorylation; Proto-Oncogene Proteins c-myc; RNA, Messenger; Tumor Suppressor Protein p53; Physiology; Molecular Biology; Cell Biology, Cell Biology, Coculture Techniques, Genomic Instability, Oxidative Phosphorylation, Proto-Oncogene Proteins c-myc, Animals, Drosophila Proteins, Drosophila, RNA, Messenger, Tumor Suppressor Protein p53, Molecular Biology, Glycolysis, Cells, Cultured, Cell Proliferation
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