論文

査読有り 筆頭著者 国際誌
2023年7月14日

Wnt Signaling Stimulates Cooperation between GREB1 and HNF4α to Promote Proliferation in Hepatocellular Carcinoma.

Cancer research
  • Shinji Matsumoto
  • ,
  • Akikazu Harada
  • ,
  • Minami Seta
  • ,
  • Masayuki Akita
  • ,
  • Hidetoshi Gon
  • ,
  • Takumi Fukumoto
  • ,
  • Akira Kikuchi

83
14
開始ページ
2312
終了ページ
2327
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/0008-5472.CAN-22-3518

UNLABELLED: 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. SIGNIFICANCE: 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.

リンク情報
DOI
https://doi.org/10.1158/0008-5472.CAN-22-3518
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/37347203
ID情報
  • DOI : 10.1158/0008-5472.CAN-22-3518
  • PubMed ID : 37347203

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