教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読なし |
表題 | Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid |
掲載誌名 | 正式名:Proceedings of the National Academy of Sciences of the United States of America 略 称:Proc Natl Acad Sci U S A ISSNコード:1091-6490(Electronic)0027-8424(Linking) |
掲載区分 | 国外 |
巻・号・頁 | 115(19),pp.4969-74 |
著者・共著者 | Qin Xian-Yang, Suzuki Harukazu, Honda Masao, Okada Hikari, Kaneko Shuichi, Inoue Ikuyo, Ebisui Etsuko, Hashimoto Kosuke, Carninci Piero, Kanki Keita, Tatsukawa Hideki, Ishibashi Naoto, Masaki Takahiro, Matsuura Tomokazu, Kagechika Hiroyuki, Toriguchi Kan, Hatano Etsuro, Shirakami Yohei, Shiota Goshi, Shimizu Masahito, Moriwaki Hisataka, Kojima Soichi |
発行年月 | 2018/05 |
概要 | Hepatocellular carcinoma (HCC) is a highly lethal cancer that has a high rate of recurrence, in part because of cancer stem cell (CSC)-dependent field cancerization. Acyclic retinoid (ACR) is a synthetic vitamin A-like compound capable of preventing the recurrence of HCC. Here, we performed a genome-wide transcriptome screen and showed that ACR selectively suppressed the expression of MYCN, a member of the MYC family of basic helix-loop-helix-zipper transcription factors, in HCC cell cultures, animal models, and liver biopsies obtained from HCC patients. MYCN expression in human HCC was correlated positively with both CSC and Wnt/β-catenin signaling markers but negatively with mature hepatocyte markers. Functional analysis showed repressed cell-cycle progression, proliferation, and colony formation, activated caspase-8, and induced cell death in HCC cells following silencing of MYCN expression. High-content single-cell imaging analysis and flow cytometric analysis identified a MYCN+ |
DOI | 10.1073/pnas.1802279115 |
PMID | 29686061 |