IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10060.html
   My bibliography  Save this article

ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1

Author

Listed:
  • Tomoya Yamaguchi

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Can Lu

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Lisa Ida

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Kiyoshi Yanagisawa

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Jiro Usukura

    (EcoTopia Science Institute, Nagoya University)

  • Jinglei Cheng

    (Nagoya University Graduate School of Medicine)

  • Naoe Hotta

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Yukako Shimada

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Hisanori Isomura

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Motoshi Suzuki

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

  • Toyoshi Fujimoto

    (Nagoya University Graduate School of Medicine)

  • Takashi Takahashi

    (Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine)

Abstract

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signalling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. Here we report an unanticipated function of this receptor tyrosine kinase (RTK) as a scaffold of cavin-1 and caveolin-1 (CAV1), two essential structural components of caveolae. This kinase-independent function of ROR1 facilitates the interactions of cavin-1 and CAV1 at the plasma membrane, thereby preventing the lysosomal degradation of CAV1. Caveolae structures and prosurvival signalling towards AKT through multiple RTKs are consequently sustained. These findings provide mechanistic insight into how ROR1 inhibition can overcome EGFR–tyrosine kinase inhibitor (TKI) resistance due to bypass signalling via diverse RTKs such as MET and IGF-IR, which is currently a major clinical obstacle. Considering its onco-embryonic expression, inhibition of the scaffold function of ROR1 in patients with lung adenocarcinoma is an attractive approach for improved treatment of this devastating cancer.

Suggested Citation

  • Tomoya Yamaguchi & Can Lu & Lisa Ida & Kiyoshi Yanagisawa & Jiro Usukura & Jinglei Cheng & Naoe Hotta & Yukako Shimada & Hisanori Isomura & Motoshi Suzuki & Toyoshi Fujimoto & Takashi Takahashi, 2016. "ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10060
    DOI: 10.1038/ncomms10060
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10060
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10060?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hirofumi Nagao & Ashok Kumar Jayavelu & Weikang Cai & Hui Pan & Jonathan M. Dreyfuss & Thiago M. Batista & Bruna B. Brandão & Matthias Mann & C. Ronald Kahn, 2023. "Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10060. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.