자유게시판

Eng Zhu and Bei Lin*AbstractBackground: 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 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 as an HE4 interacting protein. HE4 and annexin PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 II binding interaction promoted ovarian cancer cell invasion and metastasis. HE4 and annexin II expression levels were significantly Methyl 2-((4-nitro-1h-pyrazol-1-yl)methyl)benzoate 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. Keywords: Ovarian cancer, Human epididymis protein 4, Annexin II, Invasion, MetastasisBackground Ovarian cancer ranks third among malignant tumors of the female reproductive system; however, it is the leading cause of cancer-related mortality, which seriously threatens women's lives and health [1,2]. Metastasis and invasion of early-stage ovarian cancer is a major factor responsible for its high mortality and poor prognosis. Therefore, elucidating the mechanisms underlying the development and progression of ovarian cancer at a molecular level is important to facilitate the early diagnosis and treatment of ovarian cancer and to improve the prognosis of patients with this disease.* Correspondence: linbei88@hotmail.com Department of Obstetrics and Gynecology, China Medical University Shengjing Hospital, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, P.R. ChinaHuman epididymis protein 4 (HE4), 2-Chloro-3-methoxyaniline also known as whey acidic protein, was first shown to be highly expressed in ovarian cancer in 1999 [3], and it was identified as a serum marker for ovarian cancer in 2003 [4]. HE4 is highly expressed in epithelial ovarian cancer, whereas it is present at low levels in normal tissues, tumor-adjacent tissues and benign tumors [3,5]. HE4 has higher sensitivity, specificity, positive likelihood ratio and negative likelihood ratio than CA125 for the diagnosis of ovarian cancer [6]. As a secreted glycoprotein [7], HE4 has a significantly lower molecular weight than CA125, which has received wide attention. However, little is known about the function of HE4, specifically the role of HE4 in the malignant biological behavior of ovarian cancer. Recent studies showed that HE4 mainly affects the invasive and metastatic ability of ovarian cancer cells [8,9]; however, the underlying mechanism remains?2014 Zhuang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (htt.