Lu Ran, Zhou Zhiqiang, Yu Wenfei, Xia Yifu, Zhi Xuting
Department of General Surgery, Qilu Hospital of Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, PR China; Department of Vascular Surgery, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui, 233004, PR China.
Department of Pathology, School of Basic Medical Sciences of Shandong University, Wen Hua Xi Road 44, Jinan, 250012, PR China.
Biochem Biophys Res Commun. 2017 Jul 22;489(2):135-141. doi: 10.1016/j.bbrc.2017.05.112. Epub 2017 May 20.
Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a member of CPEB family which is overexpressed in variety of cancers. However, the biological role and regulatory mechanism of CPEB4 in cancers remain unknown. Here, we first investigate the role of CPEB4 in breast cancer progression and metastasis. The expression of CPEB4 is elevated in breast cancer tissues compared with adjacent normal tissues. Furthermore, high expression levels of CPEB4 is associated with tumor metastasis in breast cancer patients. Ectopic expression of CPEB4 dramatically promotes EMT, migration and invasion of breast cancer cells, while silencing CPEB4 expression significantly reduces these events. Mechanically, overexpression of CPEB4 upregulates Vimentin expression and silencing Vimentin expression blocks CPEB4-induced migration and invasion of breast cancer cells. These results implicate the potential role of CPEB4 and Vimentin in breast cancer metastasis, which is further confirmed by the finding that there is a physical interaction between the two proteins. Altogether, our results provide a novel insight into CPEB4 in regulating breast cancer progression and metastasis.
细胞质聚腺苷酸化元件结合蛋白4(CPEB4)是CPEB家族的成员之一,在多种癌症中过表达。然而,CPEB4在癌症中的生物学作用和调控机制仍不清楚。在此,我们首先研究CPEB4在乳腺癌进展和转移中的作用。与相邻正常组织相比,CPEB4在乳腺癌组织中的表达升高。此外,CPEB4的高表达水平与乳腺癌患者的肿瘤转移相关。CPEB4的异位表达显著促进乳腺癌细胞的上皮-间质转化、迁移和侵袭,而沉默CPEB4表达则显著减少这些现象。机制上,CPEB4的过表达上调波形蛋白的表达,而沉默波形蛋白的表达则阻断CPEB4诱导的乳腺癌细胞迁移和侵袭。这些结果表明CPEB4和波形蛋白在乳腺癌转移中具有潜在作用,这一发现进一步证实了这两种蛋白之间存在物理相互作用。总之,我们的结果为CPEB4在调节乳腺癌进展和转移方面提供了新的见解。