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
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

e2301977

Subventions

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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Auteurs

Qing Zhong (Q)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Hua-Gen Wang (HG)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Ji-Hong Yang (JH)

BoYu Intelligent Health Innovation Laboratory, Hangzhou, 311100, P. R. China.

Ru-Hong Tu (RH)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

An-Yao Li (AY)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.

Gui-Rong Zeng (GR)

Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.

Qiao-Ling Zheng (QL)

Diagnostic Pathology Center, Fujian Medical University, Fuzhou, 350001, P. R. China.

Zhi- Yu Liu (Z)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Zhi-Xin Shang-Guan (ZX)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Xiao- Bo Huang (X)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Qiang Huang (Q)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Yi-Fan Li (YF)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Hua-Long Zheng (HL)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Guang-Tan Lin (GT)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Ze-Ning Huang (ZN)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Kai-Xiang Xu (KX)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Wen-Wu Qiu (WW)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Mei-Chen Jiang (MC)

Diagnostic Pathology Center, Fujian Medical University, Fuzhou, 350001, P. R. China.

Ya-Jun Zhao (YJ)

Department of Gastrointestinal Surgery, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, P. R. China.

Jian-Xian Lin (JX)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Zhi-Hong Huang (ZH)

Public Technology Service Center, Fujian Medical University, Fuzhou, 350122, P. R. China.

Jing-Min Huang (JM)

Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810000, P. R. China.

Ping Li (P)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Jian-Wei Xie (JW)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Chao-Hui Zheng (CH)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Qi-Yue Chen (QY)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Chang-Ming Huang (CM)

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, P. R. China.
Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, P. R. China.

Classifications MeSH