title: TRAF4 enhances oral squamous cell carcinoma cell growth, invasion and migration by Wnt-β-catenin signaling pathway.
abstract: Oral squamous cell carcinoma (OSCC) ranks as the fifth most common cancer worldwide with poor prognosis. Recently, tumor necrosis factor receptor-associated factor 4 (TRAF4) has attracted increasing attenuation due to its overexpression in certain cancers. However, its function and underlying mechanism in OSCC remains elusive. In this study, the high expression of TRAF4 mRNA and protein levels was noted in OSCC cell lines. Its overexpression with pcDNA3.1-TRAF4 vector transfection dramatically promoted cell proliferation and inhibited cell apoptosis, indicating a pivotal role of TRAF4 in OSCC cell growth. Simultaneously, TRAF4 elevation also increased cell invasion and migration. Mechanism analysis confirmed that TRAF4 up-regulation induced the expression of β-catenin and the downstream target molecules of cyclinD1, c-myc, Bcl-2, MMP-9 and MMP-2, indicating that TRAF4 could induce the activation of Wnt/β-catenin pathway. After pretreatment with β-catenin siRNA, the pathway was remarkably silenced. Simultaneously, cell growth, invasion and migration induced by TRAF4 were strikingly abrogated, suggesting that TRAF4 may promote OSCC cell growth, invasion and migration by Wnt/β-catenin pathway. Together, this study confirmed that TRAF4 acts as an oncogene for the development and progression of OSCC. Therefore, our study may support a promising therapeutic target for the treatment of OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medial University Weihui 453100, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D000077195:Squamous Cell Carcinoma of Head and Neck; D053449:TNF Receptor-Associated Factor 4 / Q000235:genetics / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C000595707:BCL2 protein, human; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D051176:beta Catenin; D019938:Cyclin D1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Oral squamous cell carcinoma; TRAF4; Wnt/β-catenin pathway; cell growth; cell invasion; cell migration