title: Wnt-11 overexpression promoting the invasion of cervical cancer cells.
abstract: Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore, Wnt-11 was positively associated with P-JNK1 expression and promoted cervical cancer cell proliferation and invasion. These observations suggest that the increased Wnt-11 expression observed in cervical cancer cells may lead to the phosphorylation and activation of JNK-1 and significantly promote tumor cell proliferation and cell migration/invasion through activation of the Wnt/JNK pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China.
authors.forename: Shizhuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China.
authors.forename: Xiaoao
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, Shenyang, Liaoning Province, 110004, China. zhangshulanbd@163.com.
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D009856:Oncogene Proteins, Viral; D051153:Wnt Proteins; C540523:Wnt11 protein, human; D048055:Mitogen-Activated Protein Kinase 8
keywords: Cell invasion; Cell proliferation; Cervical cancer; HR-HPV E6; Wnt-11