Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells

Molecular Cancer

Research

Huiyu Zhuang¹  Mingzi Tan¹  Zhenhua Hu¹  Juanjuan Liu¹  Jian Gao¹  Dawo Liu¹  Liancheng Zhu¹  Bei Lin¹ 

[1] Department of Obstetrics and Gynecology, China Medical University Shengjing Hospital, No. 36 Sanhao Street, Heping District, 110004, Shenyang, Liaoning Province, P.R. China;

关键词: Ovarian cancer;    Human epididymis protein 4;    Annexin II;    Invasion;    Metastasis;   

DOI  :  10.1186/1476-4598-13-243

 received in 2014-04-01, accepted in 2014-10-19,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis.MethodsHE4 interacting proteins were identified by mass spectrometry and validated by co-immunoprecipitation and pull-down assays. The scratch test, the Transwell assay and animal experiments were used to assess the invasive and metastatic abilities of ovarian cancer cells before and after transfection and HE4 protein treatment. HE4 and annexin II protein expression in epithelial ovarian tissues was detected by immunohistochemistry, and the relation between their expression levels was examined.ResultsAnnexin II was identified as an HE4 interacting protein. HE4 and annexin II binding interaction promoted ovarian cancer cell invasion and metastasis. HE4 and annexin II expression levels were significantly higher in malignant epithelial ovarian tissues than in benign and normal epithelial ovarian tissues, and they were higher in tissues with lymph node metastases than in those without. HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect.ConclusionThe binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis.

【 授权许可】

Unknown   
© Zhuang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.