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Krt5+/Krt15+ foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress

Author

Listed:
  • Hyeongsun Moon

    (Cornell University)

  • Jerry Zhu

    (Cornell University)

  • Leanne R. Donahue

    (Cornell University)

  • Eunju Choi

    (University of California Davis)

  • Andrew C. White

    (Cornell University)

Abstract

The effective prevention of tumor initiation, especially for potentially inoperable tumors, will be beneficial to obtain an overall higher quality of our health and life. Hence, thorough understanding of the pathophysiological mechanisms of early tumor formation arising from identifiable cellular origins is required to develop efficient preventative and early treatment options for each tumor type. Here, using genetically engineered mouse models, we provide preclinical experimental evidence for a long-standing open question regarding the pathophysiological potential of a microenvironmental and physiological stressor in tumor development, gastric acid-mediated regional microscopic injury in foregut squamous epithelia. This study demonstrates the association of gastric acid stress with Cyclooxygenase-2-dependent tumor formation originating from tumor-competent Krt5+/Krt15+ foregut basal progenitor cells. Our findings suggest that clinical management of microenvironmental stressor-mediated microscopic injury may be important in delaying tumor initiation from foregut basal progenitor cells expressing pre-existing tumorigenic mutation(s) and genetic alteration(s).

Suggested Citation

  • Hyeongsun Moon & Jerry Zhu & Leanne R. Donahue & Eunju Choi & Andrew C. White, 2019. "Krt5+/Krt15+ foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10194-0
    DOI: 10.1038/s41467-019-10194-0
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    Cited by:

    1. 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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