title: Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability.
abstract: 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.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: de la Cova
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA; Department of Life Science and Medical BioScience, School of Advanced Science and Engineering, Waseda University, 2-2 Waskamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Nanami
authors.initials: N
authors.lastname: Senoo-Matsuda
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA; Department of Experimental Pathology, University of Bologna, 40126 Bologna, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ziosi
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.
authors.forename: D Christine
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Bellosta
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA. Electronic address: lj180@columbia.edu.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006019:Glycolysis; D010085:Oxidative Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53