Targeting Cadherin-17 Inactivates Wnt Signaling and Inhibits Tumor Growth in Liver Carcinoma
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摘要Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of beta-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma. Conclusion: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy. (HEPATOLOGY 2009;50:1453-1463.)
著者Liu LX, Lee NP, Chan VW, Xue W, Zender L, Zhang CS, Mao M, Dai HY, Wang XL, Xu MZ, Lee TK, Ng IO, Chen YC, Kung HF, Lowe SW, Poon RTP, Wang JH, Luk JM
期刊名稱Hepatology
出版年份2009
月份11
日期1
卷號50
期次5
出版社Wiley: 12 months
頁次1453 - 1463
國際標準期刊號0270-9139
電子國際標準期刊號1527-3350
語言英式英語
Web of Science 學科類別Gastroenterology & Hepatology; GASTROENTEROLOGY & HEPATOLOGY

上次更新時間 2020-29-11 於 00:32