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Endocrinology

Tumor Suppressor Role of Notch-1 Signaling in Neuroendocrine Tumors

Endocrine Surgery Research Laboratories, Department of Surgery, The University of Wisconsin, and the University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, USA

Key Words. Carcinoid • Medullary thyroid cancer • Notch-1 signaling • Achaete-scute complex-like 1 • Notch-1–activating compound

Correspondence: Herbert Chen, M.D., University of Wisconsin, H4/750 Clinical Science Center, 600 Highland Avenue, Madison, Wisconsin, 53792, USA. Telephone: 608-263-1387; Fax: 608-263-7652; e-mail: chen{at}surgery.wisc.edu

A growing body of literature is demonstrating that Notch signaling is a more complex process than originally thought. Contradictory findings of notch-1 acting as an oncogene or a tumor suppressor revealed that its role is very specific to the cellular context. In this review we focus on the tumor suppressor role of Notch-1 signaling in neuroendocrine tumors (NETs) such as carcinoid and medullary thyroid cancers. NETs secrete various bioactive hormones that can cause debilitating symptoms. Surgery is the only potential curative treatment for the patients with NETs. Notch-1 signaling is absent in these tumors and activation of Notch-1 significantly reduces tumor growth in vitro. Therefore, identification of compound(s) that activate the Notch-1 pathway in NETs could be a potential strategy to treat patients with NETs.

Disclosure of potential conflicts of interest is found at the end of this article.

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