title: CXCR7 signaling induced epithelial-mesenchymal transition by AKT and ERK pathways in epithelial ovarian carcinomas.
abstract: Epithelial-mesenchymal transition (EMT) plays an important role in oncogenesis, through which cancer cells acquire an invasion and metastasis capacity. Notably, the chemokine receptor CXCR7 and its ligands CCL19 can also facilitate lymph node metastasis in epithelial ovarian carcinomas. Here, we assumed that CXCR7 might be involved in the EMT process of epithelial ovarian carcinomas. In our study, CXCR7 activation and inhibition in SKOV3 were induced with exogenous CCL19 and CXCR7 small interfering RNA (CXCR7 siRNA), respectively. AKT and ERK protein of CXCR7 pathways as well as biomarkers (vimentin, snail, N-cadherin, and E-cadherin) of EMT were detected using the Western blot. Our results showed that CCL19 can induce AKT and ERK phosphorylation in a dose-dependent fashion; however, CXCR7 siRNA efficaciously suppressed CCL19-induced AKT and ERK phosphorylation in comparison with control siRNA. Importantly, CCL19 alone treatment can upregulate the expression of vimentin, snail, and N-cadherin of SKOV3 and downregulate the expression of E-cadherin. Conversely, knockdown of CXCR7 did not reveal any changes compared with CCL19 and the control. In conclusion, these findings demonstrate that EMT can be regulated by the CCL19/CXCR7 axis in epithelial ovarian carcinomas and then involved in the tumor cell invasion and metastasis process via activation of AKT and ERK pathways. Our study lays a new foundation for the treatment of epithelial ovarian carcinomas through antagonizing CXCR7.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, No. 107 West Wenhua Road, Jinan, 250012, Shandong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.forename: Peishu
authors.initials: P
authors.lastname: Liu
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C501896:ACKR3 protein, human; C515460:CCL19 protein, human; D015820:Cadherins; D054415:Chemokine CCL19; D054387:Receptors, CXCR; D051057:Proto-Oncogene Proteins c-akt