Haddon Lacey, Hugh Judith
Department of Laboratory of Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
Clin Exp Metastasis. 2015 Apr;32(4):393-403. doi: 10.1007/s10585-015-9711-8. Epub 2015 Mar 11.
Breast cancer is the most common cancer in women with the leading cause of death being metastasis, the spread of cancer to distant organs. For those patients with high-risk estrogen receptor positive (ER+) breast cancer, an increased expression of the glycoprotein MUC1 is associated with resistance to anti-hormonal therapy, metastasis and death. Tumor cells may use MUC1 to metastasize by exploiting the vascular adhesion pathways used by leukocytes during the inflammatory response. MUC1 is a type 1 transmembrane protein whose cytoplasmic tail acts as a scaffold for several signaling pathways including the non-receptor kinase Src, a signaling molecule involved in cell differentiation, proliferation, adhesion and motility. This review will highlight our current knowledge of how MUC1/ICAM-1 binding can lead to the recruitment and activation of Src and propose a novel role for lipid raft microdomains in this promigratory signaling. Improved understanding of the mechanism of metastases and the underlying signaling cascade is a prerequisite to the discovery of therapeutic targets to prevent metastasis and death in ER+ breast cancer patients.
乳腺癌是女性中最常见的癌症，其主要死因是转移，即癌症扩散至远处器官。对于那些高危雌激素受体阳性（ER+）乳腺癌患者，糖蛋白MUC1表达增加与抗激素治疗耐药、转移及死亡相关。肿瘤细胞可能通过利用炎症反应期间白细胞所使用的血管黏附途径，借助MUC1进行转移。MUC1是一种1型跨膜蛋白，其胞质尾部作为包括非受体激酶Src在内的多种信号通路的支架，Src是一种参与细胞分化、增殖、黏附和运动的信号分子。本综述将重点介绍我们目前对MUC1/ICAM-1结合如何导致Src的募集和激活的认识，并提出脂筏微区在这种促迁移信号传导中的新作用。更好地理解转移机制及潜在的信号级联反应是发现预防ER+乳腺癌患者转移和死亡的治疗靶点的先决条件。
