Liu, L. X., Lee, N. P. , Chan, V. W. , Xue, W., Zender, L., Zhang, C., Mao, M., Dai, H., Wang, X. L., Xu, M. Z. , Lee, T. K. , Ng, I. O. , Chen, Y., Kung, H.-f. , Lowe, S. W. , Poon, R. T. P. , Wang, J. H., Luk, J. M. (November 2009) Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology, 50 (5). pp. 1453-1463. ISSN 1527-3350
Abstract
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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > liver cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > DNA Sequencing Service |
| Depositing User: | Matt Covey |
| Date: | November 2009 |
| Date Deposited: | 15 Feb 2013 20:00 |
| Last Modified: | 30 Dec 2014 16:20 |
| PMCID: | PMC3328302 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27467 |
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