Reciprocal interaction of Wnt and RXR-α pathways in hepatocyte development and hepatocellular carcinoma

PloS One
Jinyu LiScott Powers

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-α pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-α gene signature categorized HCCs into two subtypes (high Wnt, low RXR-α and low Wnt, high RXR-α), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-α levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-α achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-α, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target.

References

Dec 7, 2002·Seminars in Cell & Developmental Biology·Stewart Sell
May 29, 2003·The Journal of Biological Chemistry·Jia-Hao XiaoRoshantha A S Chandraratna
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christine OvejeroChristine Perret
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sandrine BoyaultJessica Zucman-Rossi
Jan 18, 2007·The Journal of Biological Chemistry·Hasan H OtuSeth J Karp
Mar 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elisa WurmbachJosep M Llovet
Sep 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Aaron D TwardJ Michael Bishop
Apr 9, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xinping TanSatdarshan P S Monga
Aug 15, 2008·Cancer Research·Derek Y ChiangJosep M Llovet
Apr 22, 2009·Nuclear Receptor Signaling·Manuel MarkPierre Chambon
Jan 8, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jesper B AndersenSnorri S Thorgeirsson
Jan 12, 2010·Annual Review of Medicine·Augusto VillanuevaJosep M Llovet
May 28, 2011·Journal of Hepatology·Augusto Villanueva, Yujin Hoshida
Nov 23, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Soo Mi KimJu-Seog Lee
Feb 22, 2012·Histopathology·Nam Jin YooSug Hyung Lee
Feb 8, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lipika GoyalAndrew X Zhu
Jun 4, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sean P ClearyDerek Y Chiang
Nov 19, 2013·Nucleic Acids Research·David CroftPeter D'Eustachio
Jan 30, 2014·Journal of Geriatric Oncology·Sanghoon LeeKyu Wan Lee

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Citations

Jan 24, 2017·Molecular and Cellular Endocrinology·Danila CuomoConcetta Ambrosino
Dec 10, 2017·Journal of Tissue Engineering and Regenerative Medicine·Maria JaramilloBasak E Uygun
Jul 12, 2016·Molecular Oncology·Lise Lotte ChristensenClaus L Andersen
Oct 13, 2017·Genome Research·Ryne C RamakerSara J Cooper
Feb 14, 2016·Molecular Cancer Therapeutics·Alicia M WatersElizabeth A Beierle

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Methods Mentioned

BETA
transfection
transgenic
PCR
electrophoresis

Software Mentioned

limma R package
Significance Analysis of Microarrays ( SAM )
GSEA
Reactome
Ingenuity
ROMA

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