Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor
Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor
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DOI：
10.1158/0008-5472.can-06-4803
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发表时间：
2007-04-15
期刊：
影响因子：
11.2
通讯作者：
Ross, Theodora S.
中科院分区：
文献类型：
--
作者：
Bradley, Sarah V.;Holland, Eric C.;Ross, Theodora S.
亨廷顿蛋白相互作用蛋白I（HIPI）是一种多结构域癌蛋白，其表达与某些肿瘤中表皮生长因子受体（EGFR）水平的增加相关。例如，HIP 1转化的成纤维细胞和HIP 1阳性乳腺癌具有升高的EGFR蛋白水平。HIPI与亨廷顿蛋白（在亨廷顿氏病中突变的蛋白质）的联合关联以及已知的EGFR在神经胶质脑肿瘤中的过表达促使我们探索HIPI在一组不同类型脑癌患者中的表达。我们在此报告HIPI在脑癌中高频率过表达，并且这种过表达与EGFR和血小板衍生生长因子受体表达相关。此外，来自脑癌患者的血清样本比年龄匹配的无脑癌对照组更频繁地含有抗HIP 1抗体。最后，我们报告说，HIPI物理协会与EGFR，这种协会是独立的脂质，网格蛋白，和肌动蛋白相互作用的HIPI域。这些发现表明，HIPI可能通过直接与受体相互作用上调或维持原发性脑肿瘤中EGFR的过表达。这种新的HIPI-EGFR相互作用可能通过网格蛋白介导的膜运输途径与或独立于HIPI调节EGFR降解。现在需要进一步研究HIPI在脑癌生物学中的功能，并验证其作为预后或预测脑肿瘤标志物的用途。
Huntingtin interacting protein I (HIPI) is a multidomain oncoprotein whose expression correlates with increased epidermal growth factor receptor (EGFR) levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1-positive breast cancers have elevated EGFR protein levels. The combined association of HIPI with huntingtin, the protein that is mutated in Huntington's disease, and the known overexpression of EGFR in glial brain tumors prompted us to explore HIPI expression in a group of patients with different types of brain cancer. We report here that HIPI is over-expressed with high frequency in brain cancers and that this overexpression correlates with EGFR and platelet-derived growth factor receptor expression. Furthermore, serum samples from patients with brain cancer contained anti-HIP1 antibodies more frequently than age-matched brain cancer-free controls. Finally, we report that HIP I physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIPI. These findings suggest that HIPI may up-regulate or maintain EGFR overexpression in primary brain tumors by directly interacting with the receptor. This novel HIPI-EGFR interaction may work with or independent of HIPI modulation of EGFR degradation via clathrin-mediated membrane trafficking pathways. Further investigation of HIPI function in brain cancer biology and validation of its use as a prognostic or predictive brain tumor marker are now warranted.