Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma

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

URL: http://www.ncbi.nlm.nih.gov/pubmed/19676131
DOI: 10.1002/hep.23143

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: http://repository.cshl.edu/id/eprint/27467

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