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Atonal homolog 1 is a tumor suppressor gene

Wouter Bossuyt1, Avedis Kazanjian, Natalie De Geest

  • 1Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium.

Plos Biology
|February 27, 2009
PubMed

Insights

The Atonal homolog 1 (Atoh1) gene acts as a tumor suppressor, inhibiting colon cancer growth by regulating cell proliferation and apoptosis. Loss of ATOH1 function is linked to colorectal cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Colon cancer is a leading cause of cancer mortality.
  • Atonal homolog 1 (Atoh1) is a transcription factor with suggested anti-oncogenic roles.

Purpose of the Study:

  • To investigate the in vivo tumor suppressor function of mouse Atoh1 and human ATOH1.
  • To explore the mechanisms by which ATOH1 antagonizes tumor formation and growth.

Main Methods:

  • Genetic knockout models in mice.
  • Molecular analyses of mouse and human cancer cell lines.
  • Investigation of the Jun N-terminal kinase signaling pathway.

Main Results:

  • Mouse Atoh1 and human ATOH1 exhibit tumor suppressor activity in vivo.
  • ATOH1 regulates cell proliferation and apoptosis, likely through the Jun N-terminal kinase pathway.
  • Loss-of-function mutations in ATOH1 are observed in colorectal cancer and Merkel cell carcinoma patients.

Conclusions:

  • ATOH1 functions as a tumor suppressor gene in vivo.
  • ATOH1 plays a critical role in preventing tumor formation and growth.
  • ATOH1 may be an early target for oncogenic mutations in differentiating tissues.

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