TY - JOUR
T1 - Huntingtin-interacting protein 1
T2 - A merkel cell carcinoma marker that interacts with c-Kit
AU - Ames, Heather M.
AU - Bichakjian, Christopher K.
AU - Liu, Grace Y.
AU - Oravecz-Wilson, Katherine I.
AU - Fullen, Douglas R.
AU - Verhaegen, Monique E.
AU - Johnson, Timothy M.
AU - Dlugosz, Andrzej A.
AU - Ross, Theodora S.
N1 - Funding Information:
We are grateful to Dr Paul Harms for sharing HIP1 and HIP1-related mRNA expression data in MCC and members of the Ross laboratory for critical review of this work. This work was supported by National Cancer Institute grants to TSR: R01 CA82363-03, R01 CA098730-01, and a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research. TSR is a Leukemia and Lymphoma Society Scholar.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2011.171
DO - 10.1038/jid.2011.171
M3 - Article
C2 - 21697888
AN - SCOPUS:80052854048
SN - 0022-202X
VL - 131
SP - 2113
EP - 2120
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -