Molecular mechanism of auto-translocation of membrane anchored EGFR ligand into the nuclear membrane and its diagnostic application of cancer

膜锚定EGFR配体自转入核膜的分子机制及其在癌症诊断中的应用

• 批准号: 22650228
• 负责人: HIGASHIYAMA Shigeki
• 金额: $ 2.13万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22650228/
• 关键词: がん細胞の特性; 膜型増殖因子; HB-EGF; amphiregulin; ER/核膜移行; レトログレード小胞輸送; 膜型プロテアーゼ; 抗がん剤抵抗性; 胃がん; epiregulin; エンドサイトーシス; 核膜移行; shedding

HB-EGF and AREG are synthesized as a membrane-anchored growth factor and expressed at the plasma membrane as pro-forms in normal cells. In some malignant tumor cells in culture, however, proHB-EGF and proAREG trans-locate at the ER/nuclear membrane, which endows resistance for anti-cancer drugs. In this study, we established mouse models bearing tumor expressing proAREG auto-translocation mutant, and showed that the tumor acquired resistance for chemotherapy in vivo. We also tried to identify C-terminal processing proteases of proHB-EGF and proAREG.

HB-EGF和AREG合成为膜锚定的生长因子，并在质膜上表示为正常细胞中的pro形成。然而，在培养中的某些恶性肿瘤细胞中，ProHB-EGF和Proareg在ER/核膜上转移，该肿瘤赋予了抗癌药物的耐药性。在这项研究中，我们建立了带有表达Proareg自动转移突变体肿瘤的小鼠模型，并表明肿瘤在体内获得了化学疗法的抗性。我们还试图识别ProHB-EGF和ProAREG的C末端加工蛋白酶。

项目成果

Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands

• DOI: 10.1093/jb/mvr068
• 发表时间: 2011-07-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Higashiyama, Shigeki;Nanba, Daisuke;Fukuda, Shinji
• 通讯作者: Fukuda, Shinji

Lysophosphatidic acid stimulates epidermal growth factor-family ectodomain shedding and paracrine signaling from human lung fibroblasts.

• DOI: 10.1111/j.1524-475x.2010.00655.x
• 发表时间: 2011-03
• 期刊: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
• 作者: Shiomi T;Boudreault F;Padem N;Higashiyama S;Drazen JM;Tschumperlin DJ
• 通讯作者: Tschumperlin DJ

Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer

双调蛋白核易位可能因胃癌化疗耐药而导致预后不良

• 发表时间: 2011
• 作者: Yoshida M;Shimura T;Fukuda S;Higashiyama S;Mizoshita T;Kataoka H;Joh T
• 通讯作者: Joh T

Insulin-induced ectodomain shedding of heparin-binding epidermal growth factor-like growth factor in adipocytes in vitro

体外脂肪细胞中胰岛素诱导肝素结合表皮生长因子样生长因子的胞外域脱落

• DOI: 10.1038/oby.2010.2
• 发表时间: 2010
• 期刊: Obesity
• 影响因子: 6.9
• 作者: T. Yamamoto;T. Suganami;M. Kiso-Narita;PA. Scherle;Y. Kamei1;M. Isobe;S. Higashiyama;Y. Ogawa
• 通讯作者: Y. Ogawa

C-terminal fragment signaling of proHB-EGF for protection of cardiac cell death

proHB-EGF C 端片段信号传导保护心肌细胞死亡

• 发表时间: 2010
• 作者: 東山繁樹;井上博文
• 通讯作者: 井上博文