Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion

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  • Akikazu Harada
    Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University
  • Shinji Matsumoto
    Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University
  • Yoshiaki Yasumizu
    Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamadaoka
  • Kensaku Shojima
    Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University
  • Toshiyuki Akama
    Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University
  • Hidetoshi Eguchi
    Gastroenterological Surgery, Graduate School of Medicine, Osaka University
  • Akira Kikuchi
    Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University

書誌事項

公開日
2021-09-30
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by/4.0/
  • http://creativecommons.org/licenses/by/4.0/
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.7554/elife.66721
公開者
eLife Sciences Publications, Ltd

説明

<jats:p>Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C–IQGAP1–MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.</jats:p>

収録刊行物

  • eLife

    eLife 10 2021-09-30

    eLife Sciences Publications, Ltd

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