Kunnimalaiyaan Muthusamy, Chen Herbert
Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
Oncologist. 2007 May;12(5):535-42. doi: 10.1634/theoncologist.12-5-535.
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.
越来越多的文献表明,Notch信号传导是一个比最初认为的更为复杂的过程。关于Notch-1作为癌基因或肿瘤抑制因子的矛盾研究结果表明,其作用在细胞环境中非常具有特异性。在本综述中,我们重点关注Notch-1信号传导在神经内分泌肿瘤(NETs),如类癌和甲状腺髓样癌中的肿瘤抑制作用。NETs分泌各种生物活性激素,可导致使人衰弱的症状。手术是NETs患者唯一可能的治愈性治疗方法。这些肿瘤中不存在Notch-1信号传导,而Notch-1的激活在体外可显著降低肿瘤生长。因此,鉴定能激活NETs中Notch-1通路的化合物可能是治疗NETs患者的一种潜在策略。