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Title
  • en Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer
Creator
Accessrights open access
Rights
Subject
  • NDC 490
Description
  • 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.
Publisher en Nature Publishing Group
Date
    Issued2016-02-08
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/61333
Relation
  • isIdenticalTo DOI https://doi.org/10.1038/ncomms10656
Journal
    • PISSN 2041-1723
      • en Nature communications
      • Volume Number7 Page Start10656
File
Oaidate 2023-07-26