Tumor suppressor ATP4B serve as a promising biomarker for worsening of gastric atrophy and poor differentiation
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ORIGINAL ARTICLE
Tumor suppressor ATP4B serve as a promising biomarker for worsening of gastric atrophy and poor differentiation Yuanming Pan1,2 · Xin Wang1 · Yuqi He1,4 · Shuye Lin2,3 · Min Zhu2 · Yangjie Li1,4 · Jianxun Wang5,6 · Jiheng Wang1 · Xianzong Ma1 · Junfeng Xu1 · Lang Yang1 · Guibin Yang8 · Jiaqiang Huang3,7 · Youyong Lu2 · Jianqiu Sheng1 Received: 1 May 2020 / Accepted: 1 September 2020 © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2020
Abstract Background Hydrogen/potassium ATPase β (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 ATP4Boverexpression 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. Keywords Gastric cancer · Malignant transformation · Mitochondrion · ATP4B
Yuanming Pan, Xin Wang, and Yuqi He have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10120-020-01128-7) contains supplementary material, which is available to authorized users. * Jiaqiang Huang [email protected]
3
College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing 100044, China
4
The Second School of Clinical Medicine, Southern Medical University, 253 Middle Industrial Avenue, Guangzhou 510282, Guangdong, China
5
School of Basic Medical Sciences, Qingdao University, Qingdao, China
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Center for Regenerative Medicine, Institute for Translational Medicine, Qingdao University, Qingdao, China
7
Cancer and Inflammation Program (CIP), Center for Cancer Research (CCR), National Cancer Institute (NCI), Frederick, MD, USA
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Department of Gastroenterology, Aerospace Clinic Medical College of Peking University, No. 15 Yuanquan Road, Haid
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