Modulation of RTK by sEcad: A putative mechanism for oncogenicity in oropharyngeal SCCs

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. Materials and 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.