title: AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma.
abstract: Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.
authors.affiliation: Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.|Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Chest Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA.
authors.forename: Millicent
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Liantang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Chongjin
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China.
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; D020741:rho GTP-Binding Proteins
keywords: AEG-1; Wnt/PCP; epithelial-mesenchymal transition; metastasis; tongue squamous cell carcinoma