小细胞肺癌中Notch1信号通路、ASCL1与EMT关系研究进展

Relationship between Notch1 signaling pathway, ASCL1 and EMT in SCLC

关键词:  SCLC  Notch1信号通路  ASCL1  EMT

Key words:  SCLC  Notch1 signaling pathway  ASCL1  EMT

摘要:

小细胞肺癌（SCLC）是人类常见恶性肿瘤之一，其具有转移率和复发率高、对初始化疗敏感、易获得化学耐药等特征。上皮-间质转化（epithelial-mesenchymal transition，EMT）是肿瘤细胞发生侵袭、转移前重要的细胞表象，EMT的发生与多种细胞因子、信号传导通路及转录因子有关。尽管Notch途径激活在非小细胞肺癌（NSCLC）中起着致癌的作用，但在神经内分泌肿瘤（neuroendocrine tumors，NET）中，Notch通路激活抑制肿瘤生长。在SCLC中，Notch1通路激活可以诱导产生E-钙黏蛋白（E-Cadherin），增强细胞的粘附，诱导间质-上皮转化，从而抑制EMT过程。ASCL1（achaete-scute complex homologue 1）是SCLC一种系特异性基因，其编码的转录因子同样具有促进神经内分泌分化、EMT的功能。Notch1信号通路可以抑制ASCL1的转录，同时也可对ASCL1进行转录后调节。因此，可通过激活Notch1信号通路、抑制ASCL1表达从而抑制SCLC的发生、侵袭和转移。

Abstract:

Small cell lung cancer (SCLC) is one of the most malignant tumors in common. It is sensitivity to the initial chemotherapy but easy to acquire chemoresistance afterwards. And it has high metastatic and recurrent rates. Epithelial-mesenchymal transition (EMT) is an important phenomenon before tumor cells invade and metastasize. The occurrence of EMT is related to various cytokines, signal pathways and transcription factors. Although the activation of Notch pathway plays a carcinogenic role in non-small cell lung cancer (NSCLC), it inhibits tumor’s growth in neuroendocrine tumors (NET). In SCLC, the activation of the Notch1 signaling pathway can induce the production of E-cadherin, enhance the adhesion of cells, induce stromal-epithelial transformation, then inhibit the process of EMT. ASCL1 (achaete-scute complex homologue 1) is a lineage-specific gene of SCLC. The transcription factors encoded by it has the function of promoting the neuroendocrine differentiation and EMT. The Notch1 signaling pathway not only curbs the transcription of ASCL1, but also carries out the posttranscriptional regulation of ASCL1. Therefore, it is possible to inhibit the occurrence, invasion and metastasis of SCLC by activating the Notch1 signaling pathway and inhibiting the expression of ASCL1.