Wnt信号通路
癌症研究
LRP6型
生物
LRP5
HMGA2型
连环蛋白
信号转导
细胞生物学
基因
遗传学
小RNA
作者
Shinji Matsumoto,Akikazu Harada,Minami Seta,Masayuki Akita,Hidetoshi Gon,Takumi Fukumoto,Akira Kikuchi
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2023-06-22
卷期号:83 (14): 2312-2327
被引量:4
标识
DOI:10.1158/0008-5472.can-22-3518
摘要
Wnt signaling is known to maintain two cell states, hepatocyte differentiation and proliferation, in hepatocellular carcinoma (HCC). On the other hand, activation of Wnt signaling in colon cancer promotes uncontrollable stereotypic proliferation, whereas cells remain undifferentiated. To elucidate the unique mode of Wnt signaling in HCC, we comprehensively investigated HCC-specific Wnt pathway target genes and identified GREB1. Wnt signaling induced expression of GREB1 coupled with HNF4α and FOXA2, master transcription factors that maintain hepatic differentiation. Moreover, GREB1 was enriched at the regulatory region of atypical HNF4α target genes, including progrowth genes, thereby stimulating HCC proliferation. Therefore, GREB1 acts as a unique mediator of versatile Wnt signaling in HCC progression, bridging the roles of the Wnt pathway in differentiation and proliferation.GREB1 is a liver cancer-specific Wnt signaling target gene that induces an oncogenic shift of HNF4α, a putative tumor suppressor, and may represent a therapeutic target in Wnt-activated hepatocellular carcinoma.
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