Reciprocal Interaction of Wnt and RXR-alpha Pathways in Hepatocyte Development and Hepatocellular Carcinoma

Li, J., Chanrion, M., Sawey, E., Wang, T., Chow, E., Tward, A., Su, Y., Xue, W., Lucito, R., Zender, L., Lowe, S. W., Bishop, J. M., Powers, S. (March 2015) Reciprocal Interaction of Wnt and RXR-alpha Pathways in Hepatocyte Development and Hepatocellular Carcinoma. PLoS One, 10 (3). e0118480. ISSN 1932-6203

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URL: http://www.ncbi.nlm.nih.gov/pubmed/25738607
DOI: 10.1371/journal.pone.0118480

Abstract

Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-alpha pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-alpha gene signature categorized HCCs into two subtypes (high Wnt, low RXR-alpha and low Wnt, high RXR-alpha), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-alpha levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-alpha achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-alpha, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > liver
diseases & disorders > cancer > cancer types > liver cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Wnt
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL labs > Lucito lab
CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 4 March 2015
Date Deposited: 13 Mar 2015 19:58
Last Modified: 13 Mar 2015 19:58
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31271

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