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NOTCH Signaling and ATOH1 in Colorectal Cancers

  • Published:
Current Colorectal Cancer Reports

Abstract

The Notch receptor signaling pathway regulates expression of the basic helix-loop-helix transcription factor ATOH1 (Math1/Hath1) to determine cell fate in the intestine. In differentiating intestinal stem cells, high levels of Notch activity specify absorptive enterocyte/colonocyte differentiation, whereas high ATOH1 activity specifies secretory (goblet, enteroendocrine, and Paneth) cell differentiation. In colorectal cancer, ATOH1 is a tumor suppressor that is silenced in most tumors, while Notch is oncogenic and often highly active in human tumors. In other gastrointestinal malignancies with features of intestinal metaplasia, such as esophageal and gastric cancers, the Notch-ATOH1 pathway becomes activated. In cancers and preneoplastic tissues that retain the ability to activate ATOH1, therapeutic targeting of this pathway can be achieved by inhibiting Notch activity (with Notch-targeting antibodies or small-molecule inhibitors of γ-secretase). Thus, targeting the Notch-ATOH1 pathway represents a novel approach to differentiation therapy in gastrointestinal cancers.

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Acknowledgments

Supported by NIH grants R01 CA142826 and R03 DK084167.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, MLC 2010, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Avedis Kazanjian & Noah F. Shroyer

  2. Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Noah F. Shroyer

  3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Noah F. Shroyer

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  1. Avedis Kazanjian
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  2. Noah F. Shroyer
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Correspondence to Avedis Kazanjian or Noah F. Shroyer.

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Kazanjian, A., Shroyer, N.F. NOTCH Signaling and ATOH1 in Colorectal Cancers. Curr Colorectal Cancer Rep 7, 121–127 (2011). https://doi.org/10.1007/s11888-011-0090-5

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  • DOI: https://doi.org/10.1007/s11888-011-0090-5

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