HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.
HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.
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DOI：
10.1038/srep45768
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发表时间：
2017-03-31
影响因子：
4.6
通讯作者：
Imai K
中科院分区：
文献类型：
--
作者：
Tsuji S;Washimi K;Kageyama T;Yamashita M;Yoshihara M;Matsuura R;Yokose T;Kameda Y;Hayashi H;Morohoshi T;Tsuura Y;Yusa T;Sato T;Togayachi A;Narimatsu H;Nagasaki T;Nakamoto K;Moriwaki Y;Misawa H;Hiroshima K;Miyagi Y;Imai K
恶性间皮瘤（MM）的高度特异性标志物的缺乏阻碍了其诊断和针对MM的分子靶向治疗的发展。在这里，我们表明一种新的粘蛋白样膜蛋白，唾液酸化蛋白HEG同源物1（HEG 1），是MM的高度特异性标志物。SKM 9 -2对MM的特异性和敏感性分别达到99%和92%，与正常组织无反应。SKM 9 -2的这种准确区分是由于HEG 1肽识别唾液酸化的O-连接聚糖。我们还发现，HEG 1的基因沉默显着抑制间皮瘤细胞的生存和增殖，这一结果表明，HEG 1可能是一个值得的功能抑制药物的目标。总而言之，我们的结果表明唾液酸化的HEG 1可能可用作MM的诊断和治疗靶点。
The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.