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| ファイル | 記述 | サイズ | フォーマット | |
|---|---|---|---|---|
| s41598-018-24969-w.pdf | 6.43 MB | Adobe PDF | 見る/開く |
| タイトル: | RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells |
| 著者: | Mitsuda, Yoshihide Morita, Ken Kashiwazaki, Gengo Taniguchi, Junichi Bando, Toshikazu  Obara, Moeka Hirata, Masahiro Kataoka, Tatsuki R. Muto, Manabu   https://orcid.org/0000-0002-3127-8203 (unconfirmed)Kaneda, Yasufumi Nakahata, Tatsutoshi Liu, Pu Paul Adachi, Souichi Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed)Kamikubo, Yasuhiko |
| 著者名の別形: | 平田, 勝啓 片岡, 竜貴 武藤, 学 中畑, 龍俊 足立, 壮一 杉山, 弘 上久保, 靖彦 |
| 発行日: | 23-Apr-2018 |
| 出版者: | Springer Nature |
| 誌名: | Scientific reports |
| 巻: | 8 |
| 論文番号: | 6423 |
| 抄録: | The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M’) consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy. |
| 著作権等: | © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| URI: | http://hdl.handle.net/2433/234185 |
| DOI(出版社版): | 10.1038/s41598-018-24969-w |
| PubMed ID: | 29686309 |
| 出現コレクション: | 学術雑誌掲載論文等 |
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