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

Hyeongsun Moon, Jerry Zhu, Leanne R. Donahue, Eun ju Choi, Andrew C. White

Research output: Contribution to journalArticle

2 Citations (Scopus)

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).

Original languageEnglish (US)
Article number2225
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Gastric Acid
Cyclooxygenase 2
Tumors
tumors
acids
Acids
Neoplasms
Stem Cells
epithelium
Wounds and Injuries
mutations
health
mice
Epithelium
Cells
Health
Mutation
cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Krt5 + /Krt15 + foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress . / Moon, Hyeongsun; Zhu, Jerry; Donahue, Leanne R.; Choi, Eun ju; White, Andrew C.

In: Nature communications, Vol. 10, No. 1, 2225, 01.12.2019.

Research output: Contribution to journalArticle

@article{bc504e46bf9c44f5b31f58e2fdbefea2,
title = "Krt5 + /Krt15 + foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress",
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).",
author = "Hyeongsun Moon and Jerry Zhu and Donahue, {Leanne R.} and Choi, {Eun ju} and White, {Andrew C.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-10194-0",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Krt5 + /Krt15 + foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress

AU - Moon, Hyeongsun

AU - Zhu, Jerry

AU - Donahue, Leanne R.

AU - Choi, Eun ju

AU - White, Andrew C.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=85065970649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065970649&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10194-0

DO - 10.1038/s41467-019-10194-0

M3 - Article

C2 - 31110179

AN - SCOPUS:85065970649

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2225

ER -