Shi Xingjuan, Li Dengwen, Wang Yujue, Liu Shiyu, Qin Juan, Wang Jun, Ran Jie, Zhang Yu, Huang Qinghai, Liu Xiangdong, Zhou Jun, Liu Min
Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, China; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Am J Pathol. 2017 Mar;187(3):679-688. doi: 10.1016/j.ajpath.2016.11.005. Epub 2017 Jan 5.
Centrosome abnormalities have been implicated in the development and progression of breast cancer. However, the molecular players involved in the above processes remain largely uncharacterized. Herein, we identify centrosomal protein 70 (Cep70) as an important factor that mediates breast cancer growth and metastasis. Cep70 is up-regulated in breast cancer tissues and cell lines, and its expression is closely correlated with several clinicopathologic variables associated with breast cancer progression. Mechanistic studies reveal that the up-regulation of Cep70 in breast cancer occurs at the mRNA level and is independent of gene amplification. Cep70 promotes breast cancer cell proliferation and colony formation in vitro and increases tumor growth in mice. In addition, Cep70 stimulates breast cancer cell migration and invasion in vitro. Bioluminescence imaging analysis further shows that Cep70 enhances breast cancer lung metastasis in mice. Together, these results demonstrate a critical role for Cep70 in the development and progression of breast cancer and have important implications in the diagnosis and therapy of this malignancy.
中心体异常与乳腺癌的发生和发展有关。然而，参与上述过程的分子机制在很大程度上仍未明确。在此，我们确定中心体蛋白70（Cep70）是介导乳腺癌生长和转移的一个重要因素。Cep70在乳腺癌组织和细胞系中上调，其表达与几个与乳腺癌进展相关的临床病理变量密切相关。机制研究表明，乳腺癌中Cep70的上调发生在mRNA水平，且与基因扩增无关。Cep70促进乳腺癌细胞在体外的增殖和集落形成，并增加小鼠体内肿瘤的生长。此外，Cep70在体外刺激乳腺癌细胞的迁移和侵袭。生物发光成像分析进一步表明，Cep70增强了小鼠乳腺癌的肺转移。总之，这些结果证明了Cep70在乳腺癌发生和发展中的关键作用，并对这种恶性肿瘤的诊断和治疗具有重要意义。
