IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-13847-2.html
   My bibliography  Save this article

Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5−CD44+ cells

Author

Listed:
  • Dah-Jiun Fu

    (Cornell University)

  • Lianghai Wang

    (Cornell University
    Shihezi University School of Medicine)

  • Fouad K. Chouairi

    (Cornell University)

  • Ian M. Rose

    (Cornell University)

  • Danysh A. Abetov

    (Cornell University)

  • Andrew D. Miller

    (Cornell University)

  • Robert J. Yamulla

    (Cornell University)

  • John C. Schimenti

    (Cornell University)

  • Andrea Flesken-Nikitin

    (Cornell University)

  • Alexander Yu. Nikitin

    (Cornell University)

Abstract

Areas of a junction between two types of epithelia are known to be cancer-prone in many organ systems. However, mechanisms for preferential malignant transformation at the junction areas remain insufficiently elucidated. Here we report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction (SCJ) epithelium results in preferential formation of metastatic poorly differentiated neoplasms, which are similar to human gastroesophageal carcinoma. Unlike transformation-resistant antral cells, SCJ cells contain a highly proliferative pool of immature Lgr5−CD44+ cells, which are prone to transformation in organoid assays, comprise early dysplastic lesions, and constitute up to 30% of all neoplastic cells. CD44 ligand osteopontin (OPN) is preferentially expressed in and promotes organoid formation ability and transformation of the SCJ glandular epithelium. OPN and CD44 overexpression correlate with the worst prognosis of human gastroesophageal carcinoma. Thus, detection and selective targeting of the active OPN-CD44 pathway may have direct clinical relevance.

Suggested Citation

  • Dah-Jiun Fu & Lianghai Wang & Fouad K. Chouairi & Ian M. Rose & Danysh A. Abetov & Andrew D. Miller & Robert J. Yamulla & John C. Schimenti & Andrea Flesken-Nikitin & Alexander Yu. Nikitin, 2020. "Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5−CD44+ cells," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13847-2
    DOI: 10.1038/s41467-019-13847-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13847-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13847-2?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. Andrea Flesken-Nikitin & Coulter Q. Ralston & Dah-Jiun Fu & Andrea J. Micheli & Daryl J. Phuong & Blaine A. Harlan & Christopher S. Ashe & Amanda P. Armstrong & David W. McKellar & Sangeeta Ghuwalewal, 2024. "Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Yunqiu Miao & Lijun Li & Ying Wang & Jiangyue Wang & Yihan Zhou & Linmiao Guo & Yanqi Zhao & Di Nie & Yang Zhang & Xinxin Zhang & Yong Gan, 2024. "Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Haidi Huang & Yu Jiang & Jiangying Liu & Dan Luo & Jianghong Yuan & Rongzi Mu & Xiang Yu & Donglei Sun & Jihong Lin & Qiyue Chen & Xinjing Li & Ming Jiang & Jianming Xu & Bo Chu & Chengqian Yin & Lei , 2024. "Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool," Nature Communications, Nature, vol. 15(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:11:y:2020:i:1:d:10.1038_s41467-019-13847-2. 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.