title: Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway.
abstract: Frizzled2 (Fzd2) is a receptor for wingless-type MMTV integration site family members (Wnts), the aberrant overexpression of which has been noted to contribute to cancer metastasis. The present study was performed to characterize the role of Fzd2 in the migration and invasion of oral squamous cell carcinomas (OSCC) in vitro. Using TSCCa cells (a tongue SCC cell line) for loss- or gain-of-function of Fzd2, we found that a forced overexpression of Fzd2 promoted TSCCa cell migration and invasion, decreased the expression of epithelial‑cadherin (E-cadherin, an epithelial marker) and increased that of vimentin, Snail Slug, matrix metalloproteinases (MMPs)-2/-9/-13 and a-disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5). By contrast, RNA interference (RNAi)-mediated knockdown of Fzd2 had opposite effects on OSCC cells. In addition, we found that the phosphorylation of signal transducer and activator of transcription-3 (STAT3) was enhanced by Fzd2 overexpression, but suppressed by Fzd2 depletion, and that STAT3‑specific shRNA attenuated Fzd2 overexpression‑induced cell invasion. In summary, the present study demonstrated that Fzd2 contributes to the migration and invasion of OSCC cells, at least partly through regulation of the STAT3 pathway. These results suggest Fzd2 as a novel therapeutic target for OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Enjiao
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Zhongfei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Changfu
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051157:Frizzled Receptors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C489742:FZD2 protein, human; D051157:Frizzled Receptors; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human