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ZEB1 induces EPB41L5 in the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance

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この文献へのリンクには次のURLを使用してください:http://hdl.handle.net/2115/64728

タイトル: ZEB1 induces EPB41L5 in the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance
著者: Hashimoto, A. 著作を一覧する
Hashimoto, S. 著作を一覧する
Sugino, H. 著作を一覧する
Yoshikawa, A. 著作を一覧する
Onodera, Y. 著作を一覧する
Handa, H. 著作を一覧する
Oikawa, T. 著作を一覧する
Sabe, H. 著作を一覧する
発行日: 2016年 9月12日
出版者: Nature Publishing Group
誌名: Oncogenesis
巻: 5
開始ページ: e259
出版社 DOI: 10.1038/oncsis.2016.60
抄録: Onset of the cancer mesenchymal program is closely associated with cancer malignancy and drug resistance. Among the different epithelial-mesenchymal transition (EMT)-associated transcriptional factors, ZEB1 has a key role in inducing the mesenchymal phenotypes and stem cell-like properties of different breast cancer cells. ARF6 and its effector AMAP1 are frequently overexpressed in breast cancer cells, and promote invasion, metastasis and drug resistance. EPB41L5 is induced during EMT, and mediates the disruption of E-cadherin-based cell-cell adhesion and the promotion of focal adhesion dynamics. Here we show that EPB41L5 is an integral component of the ARF6-based pathway, which is induced by ZEB1. We found that EPB41L5 is expressed at high levels in malignant breast cancer cells and binds to AMAP1. ZEB1 induced EPB41L5 both in cancer cells and normal cells. This relationship was recaptured with The Cancer Genome Atlas RNASeq data set, and correlated with the poor outcome of the patients. In contrast, diversified events, such as tumor growth factor beta 1 stimulation, expression of SNAI1 and TP53 mutation, can each cause the induction of ZEB1 and EPB41L5, depending on the cellular context. Our results demonstrated that the ZEB1-EPB41L5 axis is at the core of the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance of significant populations of primary breast cancers, and is tightly correlated with the poor outcomes of patients.
資料タイプ: article
URI: http://hdl.handle.net/2115/64728
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 佐邊 壽孝

 

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