Cargando…

ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis

Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic rep...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Bin, Wang, Minggang, Hou, Nengyi, Hu, Xiao, Jia, Guiqing, Qin, Xianpeng, Zuo, Xiaofei, Liu, Yang, Luo, Kun, Song, Wei, Wang, Kang, Pang, Minghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840290/
https://www.ncbi.nlm.nih.gov/pubmed/27108387
http://dx.doi.org/10.1016/j.neo.2016.03.001
_version_ 1782428255723192320
author Luo, Bin
Wang, Minggang
Hou, Nengyi
Hu, Xiao
Jia, Guiqing
Qin, Xianpeng
Zuo, Xiaofei
Liu, Yang
Luo, Kun
Song, Wei
Wang, Kang
Pang, Minghui
author_facet Luo, Bin
Wang, Minggang
Hou, Nengyi
Hu, Xiao
Jia, Guiqing
Qin, Xianpeng
Zuo, Xiaofei
Liu, Yang
Luo, Kun
Song, Wei
Wang, Kang
Pang, Minghui
author_sort Luo, Bin
collection PubMed
description Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic reprogramming, which are potently associated with various cancers, play a role in H. pylori-induced gastric carcinogenesis is largely unknown. Here we revealed that Lon protease (Lonp1), which is a key inductive of mitochondrial unfolded protein response (UPR(mt)) and is required to maintain the mitochondrial quality, was greatly induced in H. pylori infected gastric epithelial cells. Importantly, we uncovered that knockdown of Lonp1 expression significantly diminished the metabolic switch to glycolysis and gastric cell proliferation associated with low multiplicity of H. pylori infection. In addition, Lonp1 overexpression in gastric epithelial cells also promoted glycolytic switch and cell overgrowth, suggesting H. pylori effect is Lonp1 dependent. We further demonstrated that H. pylori induced Lonp1 expression and cell overgrowth, at least partially, via HIF-1α regulation. Collectively, our results concluded the relevance of Lonp1 for cell proliferation and identified Lonp1 as a key regulator of metabolic reprogramming in H. pylori-induced gastric carcinogenesis.
format Online
Article
Text
id pubmed-4840290
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Neoplasia Press
record_format MEDLINE/PubMed
spelling pubmed-48402902016-05-03 ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis Luo, Bin Wang, Minggang Hou, Nengyi Hu, Xiao Jia, Guiqing Qin, Xianpeng Zuo, Xiaofei Liu, Yang Luo, Kun Song, Wei Wang, Kang Pang, Minghui Neoplasia Original article Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic reprogramming, which are potently associated with various cancers, play a role in H. pylori-induced gastric carcinogenesis is largely unknown. Here we revealed that Lon protease (Lonp1), which is a key inductive of mitochondrial unfolded protein response (UPR(mt)) and is required to maintain the mitochondrial quality, was greatly induced in H. pylori infected gastric epithelial cells. Importantly, we uncovered that knockdown of Lonp1 expression significantly diminished the metabolic switch to glycolysis and gastric cell proliferation associated with low multiplicity of H. pylori infection. In addition, Lonp1 overexpression in gastric epithelial cells also promoted glycolytic switch and cell overgrowth, suggesting H. pylori effect is Lonp1 dependent. We further demonstrated that H. pylori induced Lonp1 expression and cell overgrowth, at least partially, via HIF-1α regulation. Collectively, our results concluded the relevance of Lonp1 for cell proliferation and identified Lonp1 as a key regulator of metabolic reprogramming in H. pylori-induced gastric carcinogenesis. Neoplasia Press 2016-04-20 /pmc/articles/PMC4840290/ /pubmed/27108387 http://dx.doi.org/10.1016/j.neo.2016.03.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Luo, Bin
Wang, Minggang
Hou, Nengyi
Hu, Xiao
Jia, Guiqing
Qin, Xianpeng
Zuo, Xiaofei
Liu, Yang
Luo, Kun
Song, Wei
Wang, Kang
Pang, Minghui
ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title_full ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title_fullStr ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title_full_unstemmed ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title_short ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis
title_sort atp-dependent lon protease contributes to helicobacter pylori-induced gastric carcinogenesis
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840290/
https://www.ncbi.nlm.nih.gov/pubmed/27108387
http://dx.doi.org/10.1016/j.neo.2016.03.001
work_keys_str_mv AT luobin atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT wangminggang atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT hounengyi atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT huxiao atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT jiaguiqing atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT qinxianpeng atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT zuoxiaofei atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT liuyang atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT luokun atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT songwei atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT wangkang atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis
AT pangminghui atpdependentlonproteasecontributestohelicobacterpyloriinducedgastriccarcinogenesis