title: Huntingtin-interacting protein 1: a Merkel cell carcinoma marker that interacts with c-Kit.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ames
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Bichakjian
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Liu
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Oravecz-Wilson
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.forename: Monique E
authors.initials: ME
authors.lastname: Verhaegen
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Johnson
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Dlugosz
authors.forename: Theodora S
authors.initials: TS
authors.lastname: Ross
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015266:Carcinoma, Merkel Cell / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015995:Prevalence; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C096896:HAP1 protein, human; C490758:Hap1 protein, mouse; D009419:Nerve Tissue Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit