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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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: | 15 Jul 2021 19:58 |
| PMCID: | PMC4349704 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31271 |
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