title: Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-κB remains obscure.
  
  
  METHODS
  We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples.
  
  
  RESULTS
  Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis.
  
  
  CONCLUSIONS
  Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.affiliation: 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [3] Oral and Cranio-maxillofacial Surgery Center, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Oral and Cranio-maxillofacial Surgery Center, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000099149:Ezrin
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D004815:Epidermal Growth Factor; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D000099149:Ezrin