Département d'Endocrinologie, Université Paris Descartes, Paris, France.
Adv Exp Med Biol. 2012;727:272-88. doi: 10.1007/978-1-4614-0899-4_21.
In recent years, a substantial body of evidence has accumulated to support the notion that signaling pathways known to be important during embryonic development play important roles in regulating self-renewing tissues and tumorigenesis. In this context, Notch signaling is now recognized as essential for maintaining progenitor/ stem cell population as well as for regulating cell lineage differentiation in the normal intestinal mucosa. Many studies have also showed that Notch signaling is constitutively activated in colorectal cancer and its inhibition is able to suppress the cell growth and sensitize cancer cells to treatment-induced apoptosis. Therefore, discovery of the role of γ-secretase in the Notch signaling activation has prompted intensive research on the potential use of γ-secretase inhibitors in the treatment of colon cancer. This chapter reviews the current understanding and research findings of the role of Notch signaling in intestinal homeostasis and colorectal cancer and discusses the possible Notch targeting approaches as novel molecular therapy for intestinal cancer.
近年来，大量证据支持这样一种观点，即已知在胚胎发育过程中起重要作用的信号通路在调节自我更新组织和肿瘤发生方面起着重要作用。在这种情况下，Notch 信号现在被认为对于维持祖细胞/干细胞群体以及调节正常肠黏膜中的细胞谱系分化是必不可少的。许多研究还表明，Notch 信号在结直肠癌中持续激活，其抑制作用能够抑制细胞生长并使癌细胞对治疗诱导的细胞凋亡敏感。因此，γ-分泌酶在 Notch 信号激活中的作用的发现促使人们对 γ-分泌酶抑制剂在结肠癌治疗中的潜在用途进行了深入研究。本章综述了 Notch 信号在肠道稳态和结直肠癌中的作用的现有认识和研究结果，并讨论了 Notch 靶向方法作为肠道癌症的新型分子治疗的可能性。
