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

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.

収録刊行物

• Nature communications

  Nature communications 7 10656-, 2016-02-08

  Nature Publishing Group

詳細情報

• CRID: 1050845763949650688
• NII論文ID: 120005743066
• HANDLE: 2115/61333
• ISSN: 20411723
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles