Elucidation of the molecular mechanisms of early breast cancer invasion and metastasis

阐明早期乳腺癌侵袭和转移的分子机制

• 批准号: 23590323
• 负责人: HASHIMOTO Ari
• 金额: $ 3.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590323/
• 关键词: 浸潤; 転移; Arf6; GEP100; EMT; p53; 乳癌; AMAP1; ArfGEF

Cancer progression by which epithelial tumor cells acquire a more motile and invasive phenotype has been closely linked to the epithelial-mesenchymal transition (EMT) process. We found that GEP100-Arf6-AMAP1 pathway is important for acquisition of mesenchymal invasive phenotypes of breast cancers and TP53 alterations link to this process. Metabolic pathway regulated by mutant p53 is required for Arf6 activation. The clinical specimens of human breast cancer showed that the expression of GEP100-Arf6-AMAP1 signal correlated with recurrence after radiotherapy. Database analysis also showed that co-incidence of TP53 mutations and the high expression of this signal pathway statistically correlate with poor survival. These results suggest that generation of the Arf6-based mesenchymal invasive pathway by TP53 alterations regulate malignant progression and appears to be crucial for poor prognosis in breast cancer.

上皮肿瘤细胞获得更具运动性和侵袭性表型的癌症进展与上皮-间充质转化（EMT）过程密切相关。我们发现GEP100-Arf6-AMAP1通路对于乳腺癌间充质侵袭性表型的获得很重要，TP53的改变与这一过程有关。Arf6的激活需要突变体p53调控的代谢途径。人类乳腺癌临床标本显示，GEP100-Arf6-AMAP1信号的表达与放疗后复发相关。数据库分析还显示，TP53突变的同时发生和该信号通路的高表达在统计学上与生存率低相关。这些结果表明，通过TP53改变产生基于arf6的间充质侵袭通路调节恶性进展，似乎对乳腺癌预后不良至关重要。

项目成果

Rab5c promotes AMAP1-PRKD2 complex formation to enhance1 integrin recycling in EGF-induced cancer invasion

Rab5c 促进 AMAP1-PRKD2 复合物形成，增强 EGF 诱导的癌症侵​​袭中 1 整合素的再循环

• 发表时间: 2012
• 期刊: J Cell Biol
• 影响因子: 7.8
• 作者: Onodera Y.;Nam J.M.;Hashimoto A.;Norman JC;Shirato H;Hashimoto S.;Sabe H.
• 通讯作者: Sabe H.

beta1 integrin recycling via AMAP1-PRKD2 complex regulated by small GTPases in cancer invasion

癌症侵袭中小 GTP 酶调节的 AMAP1-PRKD2 复合物促进 beta1 整合素回收

• 发表时间: 2012
• 作者: Yasuhito Onodera; Jin-Min Nam;Ari Hashimoto;Hiroki Shirato;Shigeru Hashimoto and Hisataka Sabe
• 通讯作者: Shigeru Hashimoto and Hisataka Sabe

Tissue morphogenesis by co-operative regulation of cellular proliferation and migration and diseases due to its breakdown

通过细胞增殖和迁移的协同调节来实现组织形态发生以及由于其分解而导致的疾病

• 发表时间: 2012
• 作者: Yasuhito Onodera;Jin-Min Nam;Ari Hashimoto;Mina Bissell;Shigeru Hashimoto;Hisataka Sabe
• 通讯作者: Hisataka Sabe

変異p53はArf6活性化経路を介した浸潤獲得形質に必須である

突变体 p53 对于通过 Arf6 激活途径获得入侵性状至关重要

• 发表时间: 2012
• 作者: 橋本あり;佐邊壽孝
• 通讯作者: 佐邊壽孝

RTKs-GEP100-Arf6-AMAP1 pathway mediates cancerous EMT in response to mutant p53 and TGFβ1 signaling

RTKs-GEP100-Arf6-AMAP1 通路响应突变 p53 和 TGFβ1 信号传导介导癌性 EMT

• 发表时间: 2012
• 作者: Hisataka Sabe;Ari Hashimoto;Hirokazu Sugino;Ayumu Yoshikawa;Yutaro Otsuka;Haruka Handa;Sizuka Mito;Hiroki Sato;Jin-Min Nam;Yasuhito Onodera and Shigeru Hashimoto
• 通讯作者: Yasuhito Onodera and Shigeru Hashimoto