Cook Mackenzie, Yu Xiao-Min, Chen Herbert
Section of Endocrine Surgery, Department of Surgery, University of Wisconsin Madison, Wisconsin.
Am J Transl Res. 2010 Feb 10;2(1):119-25.
The Notch pathway plays an important role in the normal development of neuroendocrine cells, including the calcitonin producing C-cells of the thyroid. This effect has been elucidated to be mediated through modulation of Achaete-Scute Complex Like 1 (ASCL1), a transcription factor associated with poor prognosis in neuroendocrine cancer. Medullary thyroid cancer (MTC) is one of the neuroendocrine cancers derived from the thyroid C-cells. The Notch pathway has been shown to be inactive in MTC which may lead to altered expression of ASCL1. Artificial induction of Notch signaling in MTC cells can suppress ASCL1 expression, the cell growth as well as hormone secreting potential. Pharmacological activation of the Notch pathway also successfully suppresses the tumor growth in an animal model, which sheds light on the targeted therapy of Notch as a potential treatment for intractable MTC.
Notch信号通路在神经内分泌细胞的正常发育中起重要作用，包括甲状腺产生降钙素的C细胞。已阐明这种作用是通过调节类Achaete-Scute复合体1（ASCL1）介导的，ASCL1是一种与神经内分泌癌预后不良相关的转录因子。甲状腺髓样癌（MTC）是源自甲状腺C细胞的神经内分泌癌之一。已证明Notch信号通路在MTC中无活性，这可能导致ASCL1表达改变。在MTC细胞中人工诱导Notch信号可抑制ASCL1表达、细胞生长以及激素分泌潜能。Notch信号通路的药理学激活在动物模型中也成功抑制了肿瘤生长，这为将Notch作为难治性MTC的潜在治疗方法进行靶向治疗提供了思路。
