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

Hashimoto Shigeru; Mikami Shuji; Sugino Hirokazu; Yoshikawa Ayumu; Hashimoto Ari; Onodera Yasuhito; Furukawa Shotaro; Handa Haruka; Oikawa Tsukasa; Okada Yasunori; Oya Mototsugu; Sabe Hisataka

タイトル	en Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer
作成者	en Hashimoto, Shigeru NRID 1000050311303 en Mikami, Shuji NRID 1000020338180 en Sugino, Hirokazu en Yoshikawa, Ayumu en Hashimoto, Ari NRID 1000060390803 en Onodera, Yasuhito NRID 1000090435561 en Furukawa, Shotaro en Handa, Haruka en Oikawa, Tsukasa NRID 1000020457055 en Okada, Yasunori NRID 1000000115221 en Oya, Mototsugu NRID 1000000213885 en Sabe, Hisataka NRID 1000040187282
アクセス権	open access
権利情報	http://creativecommons.org/licenses/by/4.0/ en Creative Commons Attribution 4.0 International
主題	NDC 490
内容注記	Abstract en 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.
出版者	en Nature Publishing Group
日付	Issued2016-02-08
言語	eng
資源タイプ	journal article
出版タイプ	VoR
資源識別子	HDL http://hdl.handle.net/2115/61333
関連	isIdenticalTo DOI https://doi.org/10.1038/ncomms10656
収録誌情報	PISSN 2041-1723 en Nature communications 巻7 開始ページ10656
ファイル	fulltext ncomms10656-s1.pdf 14.85 MB (application/pdf) Issued2016-02-08 fulltext ncomms10656.pdf 2.47 MB (application/pdf) Issued2016-02-08
コンテンツ更新日時	2023-07-26