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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

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

Authors: Huiyu Zhuang, Mingzi Tan, Juanjuan Liu, Zhenhua Hu, Dawo Liu, Jian Gao, Liancheng Zhu, Bei Lin

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

The 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.

Methods

HE4 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.

Results

Annexin 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.

Conclusion

The binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis.
Appendix
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Metadata
Title
Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells
Authors
Huiyu Zhuang
Mingzi Tan
Juanjuan Liu
Zhenhua Hu
Dawo Liu
Jian Gao
Liancheng Zhu
Bei Lin
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-243

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