MUC1与肿瘤：信号通路和临床研究

MUC1 and tumor：signaling pathways and clinical research

摘要:

MUC1是一种异源二聚体跨膜糖蛋白，由氮端亚单位（MUC1-N）和碳端亚单位（MUC1-C）组成。MUC1在多种上皮来源的肿瘤组织中异常表达，其与肿瘤的发生发展密切相关。MUC1-N可与细胞间黏附分子-1、E-选择素和半乳凝素-3相互作用并且通过MUC1-C调节信号传导，MUC1-C可与表皮生长因子受体家族和其他酪氨酸激酶受体相互作用并且参与PI3K→AKT、MAP、NF-κB、Wnt、STAT、P53和Erα信号通路，因此MUC1与肿瘤的增殖、侵袭转移和化疗耐药密切相关。本研究阐述了MUC1-N和MUC1-C与其他分子相互作用以及在激活肿瘤相关信号通路中的作用，最后回顾了MUC1-N单抗、MUC1-C小分子肽和MUC1疫苗在临床试验阶段的研究情况。

Abstract:

MUC1 is a heterodimeric transmembrane glycoprotein formed by two subunits（N terminal and C terminal）. MUC1 is aber－rantly overexpressed in the epithelium originated tumor and is closely related to tumor development. MUC1-N interacts with ICAM-1，E-selectin and Galectin-3 and mediates signal transduction through MUC1-C；MUC1-C interacts with ErbB and other receptor tyro－sine kinases and engages in the PI3K→AKT，MAP，NF-κB，Wnt，STAT，P53 and Erα pathways，resulting in tumor proliferation，inva－sion and migration and chemoresistance. We review the role of MUC1-N and MUC1-C in interacting with other molecules and acti－vating signaling pathways. Finally，we review the clinical trials of the therapies of MUC1-N monoclonal antibodies，MUC1-C small molecule peptides and MUC1 vaccines.