title: Cell competition: winning out by losing notch.
abstract: Cell competition where 'loser' cells are eliminated by neighbors with higher fitness is a widespread phenomenon in development. However, a growing body of evidence argues cells with somatic mutations compete with their wild type counterparts in the earliest stages of cancer development. Recent studies have begun to shed light on the molecular and cellular mechanisms that alter the competitiveness of cells carrying somatic mutations in adult tissues. Cells with a 'winner' phenotype create clones which may expand into extensive fields of mutant cells within normal appearing epithelium, favoring the accumulation of further genetic alterations and the evolution of cancer. Here we focus on how mutations which disrupt the Notch signaling pathway confer a 'super competitor' status on cells in squamous epithelia and consider the broader implications for cancer evolution.
authors.affiliation: a MRC Cancer Unit; University of Cambridge; Hutchison/MRC Research Center; Cambridge Biomedical Campus ; Cambridge , UK.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Alcolea
authors.forename: Philip H
authors.initials: PH
authors.lastname: Jones
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C486455:Maml1 protein, mouse; D009687:Nuclear Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53
keywords: DD, Cell division producing 2 differentiated cells; DN-Maml1, Dominant negative mutant of Mastermind like 1; EE, Esophageal Epithelium; EYFP, Enhanced Yellow Fluorescent Protein; GFP, Green Fluorescent protein; Nicd, Notch Cytoplasmic Domain; PD, Cell division producing one progenitor and one differentiating cell; PP, Cell division producing 2 progenitor cells; cancer; carcinogenesis; esophagus; field change; progenitor; squamous; stem cell