Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY, USA.
J Exp Med. 2011 Sep 26;208(10):1931-5. doi: 10.1084/jem.20111855.
Notch signaling is often considered a model hematopoietic proto-oncogene because of its role as the main trigger of T cell acute lymphoblastic leukemia (T-ALL). Although its role in T-ALL is well characterized and further supported by a high frequency of activating NOTCH1 mutations in T-ALL patients, it still remains an open question whether the effects of Notch signaling are causative in other types of cancer, including solid tumors. Growing evidence supported by recent studies unexpectedly shows that Notch signaling can also have a potent tumor suppressor function in both solid tumors and hematological malignancies. We discuss the intriguing possibility that the pleiotropic functions of Notch can be tumor suppressive or oncogenic depending on the cellular context.
Notch 信号通路通常被认为是造血原癌基因的模型，因为它是 T 细胞急性淋巴细胞白血病 (T-ALL) 的主要触发因素。尽管 Notch 在 T-ALL 中的作用已经得到很好的描述，并且 Notch1 突变在 T-ALL 患者中的高频率进一步支持了这一作用，但 Notch 信号通路在其他类型的癌症（包括实体瘤）中的作用是否具有因果关系仍存在争议。最近的研究提供了越来越多的证据表明，Notch 信号通路在实体瘤和血液恶性肿瘤中也具有强大的肿瘤抑制功能。我们讨论了 Notch 的多效性功能可能根据细胞环境具有肿瘤抑制或致癌作用的这一有趣可能性。
