GeP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion
Masaki Morishige, Shigeru Hashimoto, Eiji Ogawa, Yoshinobu Toda, Hirokazu Kotani, Mayumi Hirose, Shumei Wei, Ari Hashimoto, Atsuko Yamada, Hajime Yano, Yuichi Mazaki, Hiroshi Kodama, Yoshinori Nio, Toshiaki Manabe, Hiromi Wada, Hidenori Kobayashi, Hisataka Sabe, NATURE CELL BIOLOGY, 10, 1, 85, U70, 2008年01月
Epidermal growth factor (EGF) receptor ( EGFR) signalling is implicated in tumour invasion and metastasis(1,2). However, whether there are EGFR signalling pathways specifically used for tumour invasion still remains elusive. Overexpression of Arf6 and its effector, AMAP1, correlates with and is crucial for the invasive phenotypes of different breast cancer cells(3-6). Here we identify the mechanism by which Arf6 is activated to induce tumour invasion. We found that GEP100/BRAG2, a guanine nucleotide exchanging factor (GEF) for Arf6, is responsible for the invasive activity of MDA-MB-231 breast cancer cells, whereas the other ArfGEFs are not. GEP100, through its pleckstrin homology domain, bound directly to Tyr1068/1086-phosphorylated EGFR to activate Arf6. Overexpression of GEP100, together with Arf6, caused non-invasive MCF7 cells(7) to become invasive, which was dependent on EGF stimulation. Moreover, GEP100 knockdown blocked tumour metastasis. GEP100 was expressed in 70% of primary breast ductal carcinomas, and was preferentially co-expressed with EGFR in the malignant cases. Our results indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive activities of some breast cancer cells, and hence may contribute to their metastasis and malignancy., NATURE PUBLISHING GROUP, 英語

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単球及び癌細胞でのパキシリンアイソフォームの発現と結合タンパク質の解析(共著)　　　　　　　　　　　　　　　
生化学雑誌, 272, 7432, 7444, 1997年

Monocyte cells and cancer cells express novel paxillin isoforms with different binding
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酵母TFIIDの変異体を用いた酸性転写活性化因子GAL4-VP16による転写活性化機構の解析(共著)　　　　　　　　　　　　　　　
自然, 369, 252, 255, 1994年

Yeast TFIID point mutants defective in activation by acidic activator GAL4-VP16　　　　　　　　　　　　　　　
Nature, 369, 252, 255, 1994年

インターロイキン6遺伝子転写調節因子(NF-IL6)(共著)　　　　　　　　　　　　　　　
化学免疫, 51, 299, 322, 1992年

A NUCLEAR FACTOR FOR THE IL-6 GENE (NF-IL6)
S AKIRA, H ISSHIKI, T NAKAJIMA, S KINOSHITA, Y NISHIO, S HASHIMOTO, S NATSUKA, T KISHIMOTO, CHEMICAL IMMUNOLOGY, 51, 299, 322, 1992年
KARGER, 英語, 書評論文,書評,文献紹介等

癌細胞の浸潤形質獲得過程の解明　　　　　　　　　　　　　　　
競争的資金

Analysis of the regulation mechanisms for the acquisition of invasive phenotype of tumor cells　　　　　　　　　　　　　　　
競争的資金