Atonal homolog 1 is a tumor suppressor gene

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix tran...

Full description

Saved in:
Bibliographic Details
Published in:PLoS biology 2009-02, Vol.7 (2), p.e39-e1000039
Main Authors: Bossuyt, Wouter, Kazanjian, Avedis, De Geest, Natalie, Van Kelst, Sofie, De Hertogh, Gert, Geboes, Karel, Boivin, Greg P, Luciani, Judith, Fuks, Francois, Chuah, Marinee, VandenDriessche, Thierry, Marynen, Peter, Cools, Jan, Shroyer, Noah F, Hassan, Bassem A
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Carcinoma, Merkel Cell - genetics
Carcinoma, Merkel Cell - metabolism
Carcinoma, Merkel Cell - pathology
Cell Line, Tumor
Cell Proliferation
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
DNA binding proteins
DNA Mutational Analysis
Drosophila
Gene Expression Regulation, Neoplastic
Genes
Genes, Tumor Suppressor - physiology
Genetic aspects
Genetics and Genomics
Health aspects
Humans
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
JNK Mitogen-Activated Protein Kinases
Kinases
Male
Mice
Mice, Knockout
Molecular Biology
Mutation
Oncology
Physiological aspects
Risk factors
Rodents
Signal Transduction
Skin Neoplasms - genetics
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Tumor suppressor genes
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.1000039