肿瘤干细胞（cancer stem cell, CSCs）不仅是肿瘤发生和转移的根源，也是导致肿瘤放、化疗失败及复发的根本原因。虽然关于CSCs的研究已有较多报道，但是CSCs如何进行自我更新仍是肿瘤研究领域尚未解决的核心问题。我们新近研究发现黏蛋白1（MUC1）高表达导致CSCs自我更新能力增强，进一步研究发现MUC1在细胞分裂中期表达并促进CSCs对称分裂，提示MUC1可能调控CSCs分裂模式进而增强CSCs自我更新能力。本项目拟在上述创新性发现的基础上，深入研究MUC1对CSCs自我更新调控的作用；揭示MUC1诱导CSCs对称分裂模式的分子机制；阐明MUC1增强CSCs自我更新在肿瘤耐药和复发中的作用。该研究将不仅揭示CSCs自我更新的新机制、创新MUC1的致癌机理，亦可望为临床靶向MUC1阳性CSCs的治疗策略提供实验依据，为肿瘤早期诊断、预防及治疗提供新思路。

Cancer stem cells (CSCs) play vital roles not only in tumor initiation and metastasis, but also in cancer therapy resistance and recurrence. While the mechanism underlying CSCs self-renew is still a central question in cancer research. Our latest preliminary data indicates that overexpression of MUC1 enhances self-renew of CSCs. Further investigation found that MUC1, which was upregulated in mitosis, related to symmetric division of CSCs. These data suggest that MUC1 may promote CSCs self-renew by regulating the metaphase proteins. The proposed work will extend our study 1) to elucidate the role of MUC1 in regulation of CSCs self-renew; 2) to figure out the mechanism of how MUC1 induced CSCs symmetric division; 3) to dissect the biological function of MUC1 in CSCs self-renew, and thereby inducing chemoresistance and recurrence of cancer. These research findings will offer new insight into CSCs self-renew and MUC1 mediated tumor initiation as well as enable the development of strategies to target MUC1 positive CSCs for cancer therapy.