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Cell competition: winning out by losing notch.


Type

Article

Change log

Authors

Alcolea, Maria P 
Jones, Philip H 

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.

Description

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, Animals, Cell Differentiation, DNA-Binding Proteins, Epithelial Cells, Esophagus, Mice, Mutation, Nuclear Proteins, Receptors, Notch, Signal Transduction, Transcription Factors, Tumor Suppressor Protein p53

Journal Title

Cell Cycle

Conference Name

Journal ISSN

1538-4101
1551-4005

Volume Title

14

Publisher

Informa UK Limited
Sponsorship
Medical Research Council (MC_UU_12022/3)
Cancer Research UK (C609/A17257)
Medical Research Council (MC_UU_12022/5)
We acknowledge the support of the MRC, the NC3Rs (National Center for the Replacement, Refinement and Reduction of Animals in Research), the Wellcome Trust (Project grant WT090334MA, to PHJ), Cancer Research UK (Program Grant C609/A17257, to PHJ) and a European Union Marie Curie Fellowship (PIEF-LIF-2007-220016, to MPA).