Loss of ATOH1 in Pit Cell Drives Stemness and Progression of Gastric Adenocarcinoma by Activating AKT/mTOR Signaling through GAS1.
ATOH1
GAS1
gastric adenocarcinoma
mouse model
stemness
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
19
08
2023
received:
29
03
2023
pubmed:
12
10
2023
medline:
12
10
2023
entrez:
12
10
2023
Statut:
ppublish
Résumé
Gastric cancer stem cells (GCSCs) are self-renewing tumor cells that govern chemoresistance in gastric adenocarcinoma (GAC), whereas their regulatory mechanisms remain elusive. Here, the study aims to elucidate the role of ATOH1 in the maintenance of GCSCs. The preclinical model and GAC sample analysis indicate that ATOH1 deficiency is correlated with poor GAC prognosis and chemoresistance. ScRNA-seq reveals that ATOH1 is downregulated in the pit cells of GAC compared with those in paracarcinoma samples. Lineage tracing reveals that Atoh1 deletion strongly confers pit cell stemness. ATOH1 depletion significantly accelerates cancer stemness and chemoresistance in Tff1-CreERT2; Rosa26
Identifiants
pubmed: 37824217
doi: 10.1002/advs.202301977
pmc: PMC10646280
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2301977Subventions
Organisme : Youth Research Planning Project of Fujian Province Health Commission Science and Technology
ID : 2023QN01010108
Organisme : National Natural Science Foundation of China
ID : 81871899
Organisme : Construction Project of Fujian Province Minimally Invasive Medical Center
ID : [2021]76
Organisme : Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital
ID : 2022XH021
Organisme : Scientific Research Foundation of Graduate School of Harbin Medical University: Sino Russian Special Fund
ID : 2020QH2028
Informations de copyright
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
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