title: Modulation of RTK by sEcad: a putative mechanism for oncogenicity in oropharyngeal SCCs.
abstract: OBJECTIVE
  Heightened levels of sEcad are found in the serum of patients with cancer and correlate with an unfavorable prognosis and later-stages of disease. In this study, we explored whether sEcad is elevated in human OPSCC specimens and FaDu cells. Additionally, we investigated sEcad-EGFR and sEcad-IGF-1R interactions and performed a functional analysis of sEcad in OPSCC cancers.
  
  
  METHODS
  sEcad, EGFR, and IGF-1R levels were examined in human OPSCC specimens and cells by immunoblotting. sEcad-EGFR and sEcad-IGF-1R interactions were examined by immunoprecipitation and immunoblot assays. Levels of sEcad on EGFR and IGF-1R pathway components were evaluated by IB. The effects of sEcad on OPSCC proliferation, migration, and invasion were assessed using standard cellular assays.
  
  
  RESULTS
  Statistical analysis demonstrated that sEcad levels were significantly higher in OPSCC primary tumors and cells compared with normal controls. IP studies indicated that sEcad associated with EGFR and IGF-1R, and addition of sEcad resulted in a statistically significant increase in downstream signaling. Finally, cell-based assays demonstrated enhanced sEcad-induced proliferation, migration, and invasion, which was blocked by EGFR and IGF-1R inhibitors.
  
  
  CONCLUSIONS
  These findings suggest that sEcad may play an important role in OPSCC oncogenicity via its interaction and activation of EGFR and IGF-1R.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, New York, USA.
authors.forename: X
authors.initials: X
authors.lastname: Teng
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Kyrkanides
authors.forename: V
authors.initials: V
authors.lastname: Raja
authors.forename: D
authors.initials: D
authors.lastname: Trochesset
authors.forename: S M
authors.initials: SM
authors.lastname: Brouxhon
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D015820:Cadherins; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1
keywords: EGFR; IGF-1R; OPSCC; sEcad