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

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

Hashimoto, Shigeru; Mikami, Shuji; Sugino, Hirokazu et al.

Nature communications, 2016, 7, 10656

Permalink : https://hdl.handle.net/2115/61333

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/61333
タイトル	Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer
著者	Hashimoto, Shigeru ; Mikami, Shuji ; Sugino, Hirokazu ; Yoshikawa, Ayumu ; Hashimoto, Ari ; Onodera, Yasuhito ; Furukawa, Shotaro ; Handa, Haruka ; Oikawa, Tsukasa ; Okada, Yasunori ; Oya, Mototsugu ; Sabe, Hisataka
e-Rad_Researcher 50311303 著者名 Hashimoto, Shigeru
e-Rad_Researcher 20338180 著者名 Mikami, Shuji
著者名 Sugino, Hirokazu
著者名 Yoshikawa, Ayumu
e-Rad_Researcher 60390803 著者名 Hashimoto, Ari
e-Rad_Researcher 90435561 著者名 Onodera, Yasuhito
著者名 Furukawa, Shotaro
著者名 Handa, Haruka
e-Rad_Researcher 20457055 著者名 Oikawa, Tsukasa
e-Rad_Researcher 00115221 著者名 Okada, Yasunori
e-Rad_Researcher 00213885 著者名 Oya, Mototsugu
e-Rad_Researcher 40187282 著者名 Sabe, Hisataka
言語	英語
発行日	2016-02-08
出版者	Nature Publishing Group
収録物名	Nature communications
巻(号)	7
ページ	10656
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	2041-1723
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1038/ncomms10656