Huntingtin-interacting protein 1: A merkel cell carcinoma marker that interacts with c-Kit

Heather M. Ames, Christopher K. Bichakjian, Grace Y. Liu, Katherine I. Oravecz-Wilson, Douglas R. Fullen, Monique E. Verhaegen, Timothy M. Johnson, Andrzej A. Dlugosz, Theodora S. Ross

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16 Scopus citations

Abstract

Merkel cell carcinoma (MCC) is a neoplasm thought to originate from the neuroendocrine Merkel cells of the skin. Although the prevalence of MCC has been increasing, treatments for this disease remain limited because of a paucity of information regarding MCC biology. We have found that the endocytic oncoprotein Huntingtin-interacting protein 1 (HIP1) is expressed at high levels in 90% of MCC tumors and serves as a more reliable histological cytoplasmic stain than the gold standard, cytokeratin 20. Furthermore, high anti-HIP1 antibody reactivity in the sera of a cohort of MCC patients predicts the presence of metastases. Another protein that is frequently expressed at high levels in MCC tumors is the stem cell factor (SCF) receptor tyrosine kinase, c-Kit. In working toward an understanding of how HIP1 might contribute to MCC tumorigenesis, we have discovered that HIP1 interacts with SCF-activated c-Kit. These data not only identify HIP1 as a molecular marker for management of MCC patients but also show that HIP1 interacts with and slows the degradation of c-Kit.

Original languageEnglish (US)
Pages (from-to)2113-2120
Number of pages8
JournalJournal of Investigative Dermatology
Volume131
Issue number10
DOIs
Publication statusPublished - Oct 2011

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ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ames, H. M., Bichakjian, C. K., Liu, G. Y., Oravecz-Wilson, K. I., Fullen, D. R., Verhaegen, M. E., ... Ross, T. S. (2011). Huntingtin-interacting protein 1: A merkel cell carcinoma marker that interacts with c-Kit. Journal of Investigative Dermatology, 131(10), 2113-2120. https://doi.org/10.1038/jid.2011.171