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Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer

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Title: Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer
Authors: Hashimoto, Shigeru Browse this author →KAKEN DB
Mikami, Shuji Browse this author →KAKEN DB
Sugino, Hirokazu Browse this author
Yoshikawa, Ayumu Browse this author
Hashimoto, Ari Browse this author →KAKEN DB
Onodera, Yasuhito Browse this author →KAKEN DB
Furukawa, Shotaro Browse this author
Handa, Haruka Browse this author
Oikawa, Tsukasa Browse this author →KAKEN DB
Okada, Yasunori Browse this author →KAKEN DB
Oya, Mototsugu Browse this author →KAKEN DB
Sabe, Hisataka Browse this author →KAKEN DB
Issue Date: 8-Feb-2016
Publisher: Nature Publishing Group
Journal Title: Nature communications
Volume: 7
Start Page: 10656
Publisher DOI: 10.1038/ncomms10656
Abstract: Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and AMAP1 then binds to the mesenchymal-specific protein EPB41L5, which promotes epithelial-mesenchymal transition and focal adhesion dynamics. In renal cancer cells, lysophosphatidic acid (LPA) activates Arf6 via its G-protein-coupled receptors, in which GTP-G alpha 12 binds to EFA6. The Arf6-based pathway may also contribute to drug resistance. Our results identify a specific mesenchymal molecular machinery of primary ccRCCs, which is triggered by a product of autotaxin and it is associated with poor outcome of patients.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/61333
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐邊 壽孝

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