Department of Anatomy, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia.
Curr Drug Targets. 2018;19(2):128-143. doi: 10.2174/1389450118666170309143419.
The Notch pathway is an evolutionarily conserved, intercellular signalling system which is present in all multicellular organisms and mammals. The Notch pathway plays an important role in the embryonic development as it controls cell proliferation, cell differentiation and binary cell fate decisions.
In the present review, we highlight the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. We also discuss the tumor biology of the Notch pathway involved in various cancers.
Interestingly, the Notch signalling pathway is dysregulated in many cancers. Notch may serve as oncogene or tumor suppressor and plays an important role in cancers of the liver, pancreas, endometrium of uterus, ovary, prostate, bladder and colon. The activation of Notch pathway plays a vital role in the progression of some cancer. In addition, Notch pathway activation was also shown to drive chemoresistance in cancer, as well. Chemotherapeutically, combined NOTCH1 inhibitor synergistically attenuated chemotherapy-enriched cancer stem cell population both in vitro and in vivo. This may prove to be beneficial in the treatment of cancer.
The Notch inhibitors possess anti-proliferative effects on cancer, thereby serving as a new treatment for cancer.
Notch 通路是一种进化上保守的细胞间信号系统，存在于所有多细胞生物和哺乳动物中。Notch 通路在胚胎发育中起着重要作用，因为它控制着细胞增殖、细胞分化和二元细胞命运决定。
在本综述中，我们重点介绍 Notch 信号通路的组成部分，即 Notch 受体、配体、效应物及其调节剂。我们还讨论了 Notch 通路在各种癌症中的肿瘤生物学。
有趣的是，Notch 信号通路在许多癌症中失调。Notch 可以作为癌基因或肿瘤抑制因子，在肝癌、胰腺癌、子宫内膜癌、卵巢癌、前列腺癌、膀胱癌和结肠癌中发挥重要作用。Notch 通路的激活在某些癌症的进展中起着至关重要的作用。此外，Notch 通路的激活也被证明能在癌症中诱导化疗耐药性。化疗药物联合使用 NOTCH1 抑制剂在体外和体内均能协同减弱化疗富集的癌症干细胞群。这在癌症治疗中可能是有益的。
Notch 抑制剂对癌症具有抗增殖作用，因此可作为癌症的新治疗方法。
