IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-13771-5.html
   My bibliography  Save this article

YAP1 mediates survival of ALK-rearranged lung cancer cells treated with alectinib via pro-apoptotic protein regulation

Author

Listed:
  • Takahiro Tsuji

    (Kyoto University)

  • Hiroaki Ozasa

    (Kyoto University)

  • Wataru Aoki

    (Kyoto University)

  • Shunsuke Aburaya

    (Kyoto University)

  • Tomoko Yamamoto Funazo

    (Kyoto University)

  • Koh Furugaki

    (Chugai Pharmaceutical Co., Ltd)

  • Yasushi Yoshimura

    (Chugai Pharmaceutical Co., Ltd)

  • Masatoshi Yamazoe

    (Kyoto University)

  • Hitomi Ajimizu

    (Kyoto University)

  • Yuto Yasuda

    (Kyoto University)

  • Takashi Nomizo

    (Kyoto University)

  • Hironori Yoshida

    (Kyoto University)

  • Yuichi Sakamori

    (Kyoto University)

  • Hiroaki Wake

    (Kobe University)

  • Mitsuyoshi Ueda

    (Kyoto University)

  • Young Hak Kim

    (Kyoto University)

  • Toyohiro Hirai

    (Kyoto University)

Abstract

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.

Suggested Citation

  • Takahiro Tsuji & Hiroaki Ozasa & Wataru Aoki & Shunsuke Aburaya & Tomoko Yamamoto Funazo & Koh Furugaki & Yasushi Yoshimura & Masatoshi Yamazoe & Hitomi Ajimizu & Yuto Yasuda & Takashi Nomizo & Hirono, 2020. "YAP1 mediates survival of ALK-rearranged lung cancer cells treated with alectinib via pro-apoptotic protein regulation," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13771-5
    DOI: 10.1038/s41467-019-13771-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13771-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13771-5?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. Chun-Hua Hung & Shang-Yin Wu & Cheng-I Daniel Yao & Hsuan-Heng Yeh & Chien-Chung Lin & Chang-Yao Chu & Tzu-Yu Huang & Meng-Ru Shen & Chun-Hung Lin & Wu-Chou Su, 2024. "Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-24, 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:11:y:2020:i:1:d:10.1038_s41467-019-13771-5. 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.