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CEACAM1-4S对乳腺癌细胞侵袭和迁移的抑制作用。

Inhibition of cell invasion and migration by CEACAM1-4S in breast cancer.

作者信息

Yang Changcheng, Cao Manlin, Liu Yiwen, He Yiqing, Yang Cuixia, Du Yan, Wang Wenjuan, Zhang Guoliang, Wu Man, Zhou Muqing, Gao Feng

机构信息

Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

Department of Rehabilitation Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

出版信息

Oncol Lett. 2017 Oct;14(4):4758-4766. doi: 10.3892/ol.2017.6791. Epub 2017 Aug 23.

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cell-cell adhesion molecule, has been revealed to perform an important role in tumor progression. Although there are a number of studies on CEACAM1 in patients with breast cancer, there is limited information on the roles of CEACAM1 in breast cancer metastasis. The present study aimed to identify whether CEACAM1 is involved in breast cancer development and to investigate the underlying mechanisms. First, the expression of CEACAM1 was observed in patients with breast cancer, and the association between CEACAM1 expression levels and migration and invasion of breast cancer cells was analyzed. As there are 12 isoforms of CEACAM1, of which CEACAM1-4S dominates in the human breast epithelium, subsequent study focused on CEACAM1-4S as a representative of all the isoforms. Results of the present study demonstrated that CEACAM1-4S suppresses breast cancer cell invasion and migration in a manner that is dependent on the balance between matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2 and E-/N-cadherin expression. In addition, CEACAM1-4S was likely to cause reversal of epithelial-mesenchymal transition of breast cancer cells through repressing Smad2 and signal transducer and phosphorylation of activator of transcription 3. In conclusion, the present study demonstrated that CEACAM1-4S performs an inhibitory role in breast cancer metastasis, and restoring CEACAM1-4S expression may provide a novel strategy for therapy of patients with metastatic breast cancer.

摘要

癌胚抗原相关细胞黏附分子1(CEACAM1)是一种细胞间黏附分子,已被揭示在肿瘤进展中发挥重要作用。尽管关于乳腺癌患者的CEACAM1已有多项研究,但关于CEACAM1在乳腺癌转移中的作用的信息有限。本研究旨在确定CEACAM1是否参与乳腺癌的发展,并探讨其潜在机制。首先,观察了乳腺癌患者中CEACAM1的表达,并分析了CEACAM1表达水平与乳腺癌细胞迁移和侵袭之间的关联。由于CEACAM1有12种异构体,其中CEACAM1-4S在人乳腺上皮中占主导地位,随后的研究集中于CEACAM1-4S作为所有异构体的代表。本研究结果表明,CEACAM1-4S以依赖基质金属蛋白酶2/金属蛋白酶组织抑制剂2平衡以及E-钙黏蛋白/N-钙黏蛋白表达的方式抑制乳腺癌细胞的侵袭和迁移。此外,CEACAM1-4S可能通过抑制Smad2以及信号转导和转录激活因子3的磷酸化导致乳腺癌细胞上皮-间质转化的逆转。总之,本研究表明CEACAM1-4S在乳腺癌转移中发挥抑制作用,恢复CEACAM1-4S的表达可能为转移性乳腺癌患者的治疗提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/5649695/47cfe0918eef/ol-14-04-4758-g00.jpg

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