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Tumor suppressor ATP4B serve as a promising biomarker for worsening of gastric atrophy and poor differentiation

  1. Author:
    Pan, Yuanming
    Wang, Xin
    He, Yuqi
    Lin, Shuye
    Zhu, Min
    Li, Yangjie
    Wang, Jianxun
    Wang, Jiheng
    Ma, Xianzong
    Xu, Junfeng
    Yang, Lang
    Yang, Guibin
    Huang, Jiaqiang
    Lu, Youyong
    Sheng, Jianqiu [ORCID]

  2. Author Address

    Department of Gastroenterology, the 7th Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing, 100700, China., Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China., The Second School of Clinical Medicine, Southern Medical University, 253 Middle Industrial Avenue, Guangzhou, 510282, Guangdong, China., College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044, China., School of Basic Medical Sciences, Qingdao University, Qingdao, China., Center for Regenerative Medicine, Institute for Translational Medicine, Qingdao University, Qingdao, China., Department of Gastroenterology, Aerospace Clinic Medical College of Peking University, No. 15 Yuanquan Road, Haidian District, Beijing, 100049, China., College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044, China. jqhuang@bjtu.edu.cn., Cancer and Inflammation Program (CIP), Center for Cancer Research (CCR), National Cancer Institute (NCI), Frederick, MD, USA. jqhuang@bjtu.edu.cn., Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China. youyonglu@hsc.pku.edu.cn., Department of Gastroenterology, the 7th Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing, 100700, China. jianqiu@263.net.,
    1. Year: 2020
    2. Date: Oct 27
    3. Epub Date: 2020 10 27
  2. Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
  4. Type of Article: Article
  5. ISSN: 1436-3291
  1. Abstract:

    Background: Hydrogen/potassium ATPase ß (ATP4B) is a proton pump acting an essential role in gastric acid secretion. This study aimed to investigate the diagnostic performance of ATP4B and its biological role in tumor progression in gastric cancer. Methods: The correlations between ATP4B expression level and clinicopathologic parameters, as well as the relevance of ATP4B expression with overall survival were assessed. The functional roles of ATP4B in gastric cancer were verified by gain- and loss-of-function cell models and tumor xenograft models. The possible downstream effects of ATP4B were analyzed by iTRAQ-based quantitative proteomics analysis. Results: A dramatic decrease in ATP4B was associated with malignant transformation in gastric mucosa lesions and correlated with poor differentiation. Restoration of ATP4B expression in gastric cancer cells significantly suppressed cell proliferation, cell viability, migration, invasion, tumorigenicity and induced apoptosis, whereas ATP4B silencing exerted the opposite effects. Mechanistically, we found a quality control on mitochondrial metabolism and functions in ATP4B-overexpression GC cells. Conclusions: Our data suggest that decreasing ATP4B is an indicator for gastric mucosa malignant transformation and GC aggressive phenotype and it plays an inhibitory role in gastric cancer as a tumor suppressor via regulating mitochondrial metabolism and apoptosis pathway.

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External Sources

  1. View Full Text
  2. DOI: 10.1007/s10120-020-01128-7
  3. PMID: 33111209
  4. View record in Web of Science®
  5. WOS: 000585620500001
  6. PII : 10.1007/s10120-020-01128-7

Library Notes

  1. Fiscal Year: FY2020-2021
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