Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Nita J. Maihle

Subject Area(s)

Oncology

Abstract

The HER3 receptor tyrosine kinase is an important member of the human epidermal growth factor (EGF) receptor family, which has received tremendous clinical success as a target in the development of cancer therapeutics. Recent studies have shown that HER3 is associated with poor prognosis in melanoma but the exact mechanisms remain to be unraveled. A secreted isoform of HER3, p85-sHER3, was previously shown by our group to inhibit neuregulin-1 mediated, Akt-dependent breast cancer cell growth in vitro. In this study, we demonstrated that p85-sHER3 inhibits melanoma cell proliferation and migration and further identified tenascin C as the major binding partner with p85-sHER3 in melanoma cell conditioned media via mass spectrometry. Together, these results suggest that p85-sHER3 likely inhibits melanoma development in a tenascin C-dependent manner. This represents a novel approach in explaining the mechanistic role(s) of EGF receptors in melanoma tumorigenesis and promises to open new avenues for drug design and counteracting drug resistance in the treatment of melanoma.

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