title: Atonal homolog 1 is a tumor suppressor gene.
abstract: 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.
authors.affiliation: Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Bossuyt
authors.forename: Avedis
authors.initials: A
authors.lastname: Kazanjian
authors.forename: Natalie
authors.initials: N
authors.lastname: De Geest
authors.forename: Sofie
authors.initials: S
authors.lastname: Van Kelst
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Greg P
authors.initials: GP
authors.lastname: Boivin
authors.forename: Judith
authors.initials: J
authors.lastname: Luciani
authors.forename: Francois
authors.initials: F
authors.lastname: Fuks
authors.forename: Marinee
authors.initials: M
authors.lastname: Chuah
authors.forename: Thierry
authors.initials: T
authors.lastname: VandenDriessche
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
authors.forename: Noah F
authors.initials: NF
authors.lastname: Shroyer
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Hassan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D048031:JNK Mitogen-Activated Protein Kinases; C500942:ATOH1 protein, human; C500943:Atoh1 protein, mouse