IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32787-y.html
   My bibliography  Save this article

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

Author

Listed:
  • Liang Ding

    (Medical School of Nanjing University)

  • Yong Fu

    (Medical School of Nanjing University)

  • Nisha Zhu

    (Medical School of Nanjing University)

  • Mengxiang Zhao

    (Medical School of Nanjing University)

  • Zhuang Ding

    (Medical School of Nanjing University)

  • Xiaoxin Zhang

    (Medical School of Nanjing University)

  • Yuxian Song

    (Medical School of Nanjing University)

  • Yue Jing

    (Medical School of Nanjing University)

  • Qian Zhang

    (Medical School of Nanjing University)

  • Sheng Chen

    (Medical School of Nanjing University)

  • Xiaofeng Huang

    (Medical School of Nanjing University)

  • Lorraine A O’Reilly

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • John Silke

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Qingang Hu

    (Medical School of Nanjing University
    Medical School of Nanjing University)

  • Yanhong Ni

    (Medical School of Nanjing University)

Abstract

The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFsWPOI4-5), characterized by high oxytocin receptor expression (OXTRHigh), contribute to local-regional metastasis. OXTRHigh CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3+ tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTRHigh CAFs. Therefore, targeting ERK5 signaling in OXTRHigh CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

Suggested Citation

  • Liang Ding & Yong Fu & Nisha Zhu & Mengxiang Zhao & Zhuang Ding & Xiaoxin Zhang & Yuxian Song & Yue Jing & Qian Zhang & Sheng Chen & Xiaofeng Huang & Lorraine A O’Reilly & John Silke & Qingang Hu & Ya, 2022. "OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32787-y
    DOI: 10.1038/s41467-022-32787-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32787-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32787-y?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
    ---><---

    References listed on IDEAS

    as
    1. Martin Baumdick & Márton Gelléri & Chayasith Uttamapinant & Václav Beránek & Jason W. Chin & Philippe I. H. Bastiaens, 2018. "A conformational sensor based on genetic code expansion reveals an autocatalytic component in EGFR activation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    2. Pamela A. Lochhead & Julie A. Tucker & Natalie J. Tatum & Jinhua Wang & David Oxley & Andrew M. Kidger & Victoria P. Johnson & Megan A. Cassidy & Nathanael S. Gray & Martin E. M. Noble & Simon J. Cook, 2020. "Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Frederik Steiert & Peter Schultz & Siegfried Höfinger & Thomas D. Müller & Petra Schwille & Thomas Weidemann, 2023. "Insights into receptor structure and dynamics at the surface of living cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Xi Wu & Fei Shen & Guanglong Jiang & Gloria Xue & Santosh Philips & Laura Gardner & Geneva Cunningham & Casey Bales & Erica Cantor & Bryan Paul Schneider, 2022. "A non-coding GWAS variant impacts anthracycline-induced cardiotoxic phenotypes in human iPSC-derived cardiomyocytes," Nature Communications, Nature, vol. 13(1), pages 1-13, 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:13:y:2022:i:1:d:10.1038_s41467-022-32787-y. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.