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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
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    Cited by:

    1. 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.
    2. 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.

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