Premium
Targeting cadherin‐17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma
Author(s) -
Liu Ling Xiao,
Lee Nikki P.,
Chan Vivian W.,
Xue Wen,
Zender Lars,
Zhang Chunsheng,
Mao Mao,
Dai Hongyue,
Wang Xiao Lin,
Xu Michelle Z.,
Lee Terence K.,
Ng Irene O.,
Chen Yangchao,
Kung Hsiangfu,
Lowe Scott W.,
Poon Ronnie T.P.,
Wang Jian Hua,
Luk John M.
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23143
Subject(s) - cadherin , wnt signaling pathway , cancer research , carcinoma , signal transduction , medicine , chemistry , biology , microbiology and biotechnology , biochemistry , cell
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 β‐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. (H EPATOLOGY 2009.)