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Modulation of RTK by sE cad: a putative mechanism for oncogenicity in oropharyngeal SCCs
Author(s) -
Teng X,
Ma L,
Kyrkanides S,
Raja V,
Trochesset D,
Brouxhon SM
Publication year - 2015
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12235
Subject(s) - mechanism (biology) , cad , modulation (music) , biology , physics , biochemistry , quantum mechanics , acoustics
Objective Heightened levels of sE cad 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 sE cad is elevated in human OPSCC specimens and FaDu cells. Additionally, we investigated sE cad‐EGFR and sE cad‐IGF‐1R interactions and performed a functional analysis of sE cad in OPSCC cancers. Materials and Methods sE cad, EGFR, and IGF‐1R levels were examined in human OPSCC specimens and cells by immunoblotting. sE cad‐EGFR and sE cad‐IGF‐1R interactions were examined by immunoprecipitation and immunoblot assays. Levels of sE cad on EGFR and IGF‐1R pathway components were evaluated by IB. The effects of sE cad on OPSCC proliferation, migration, and invasion were assessed using standard cellular assays. Results Statistical analysis demonstrated that sE cad levels were significantly higher in OPSCC primary tumors and cells compared with normal controls. IP studies indicated that sE cad associated with EGFR and IGF‐1R, and addition of sE cad resulted in a statistically significant increase in downstream signaling. Finally, cell‐based assays demonstrated enhanced sE cad‐induced proliferation, migration, and invasion, which was blocked by EGFR and IGF‐1R inhibitors. Conclusions These findings suggest that sE cad may play an important role in OPSCC oncogenicity via its interaction and activation of EGFR and IGF‐1R.