Helicobacter pylori promotes gastric cancer progression by activating the TGF-β/Smad2/EMT pathway through HKDC1

被引：5
作者：
Fang, Ziqing [1 ]
Zhang, Weitong [2 ]
Wang, Huizhen [1 ]
Zhang, Chaoyang [3 ]
Li, Jing [1 ]
Chen, Wanjing [1 ]
Xu, Xin [1 ]
Wang, Luyang [1 ]
Ma, Mengdi [1 ]
Zhang, Shangxin [1 ]
Li, Yongxiang [1 ]
机构：
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Gen Surg, 218 JiXi Ave, Hefei 230022, Anhui, Peoples R China
[2] Yijishan Hosp, Wannan Med Coll, Dept Gen Surg, Wuhu 241001, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 2, Dept Gen Surg, Hangzhou 310000, Peoples R China
来源：
CELLULAR AND MOLECULAR LIFE SCIENCES | 2024年 / 81卷 / 01期
基金：
中国国家自然科学基金;
关键词：
TFF1; H; pylori; Gastric cancer mouse model; Galunisertib; HEXOKINASE; LOCALIZATION; MECHANISMS; INFECTION; TFF1;
D O I：
10.1007/s00018-024-05491-x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Helicobacter pylori (H. pylori) infection is widely acknowledged as the primary risk factor for gastric cancer, facilitating its progression via the Correa cascade. Concurrently, Hexokinase Domain Containing 1 (HKDC1) has been implicated in the mediation of aerobic glycolysis, contributing to tumorigenesis across various cancers. However, the precise role of HKDC1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains elusive. In this study, transcriptome sequencing revealed a significant correlation between HKDC1 and H. pylori-induced gastric cancer. Subsequent validation using qRT-PCR, immunohistochemistry, and Western blot analysis confirmed elevated HKDC1 expression in both human and murine gastritis and gastric tumors. Moreover, in vitro and in vivo experiments demonstrated that H. pylori infection up-regulates TGF-beta 1 and p-Smad2, thereby activating the epithelial-mesenchymal transition (EMT) pathway, with HKDC1 playing a pivotal role. Suppression of HKDC1 expression or pharmacological inhibition of TGF-beta 1 reversed EMT activation, consequently reducing gastric cancer cell proliferation and metastasis. These results underscore HKDC1's essential contribution to H. pylori-induced gastric cancer progression via EMT activation.
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页数：17
相关论文
共 41 条
[1]   Pathobiology of Helicobacter pylori-Induced Gastric Cancer [J].
Amieva, Manuel ;
Peek, Richard M., Jr. .
GASTROENTEROLOGY, 2016, 150 (01) :64-78
[2]   Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer [J].
Baj, Jacek ;
Korona-Glowniak, Izabela ;
Forma, Alicja ;
Maani, Amr ;
Sitarz, Elzbieta ;
Rahnama-Hezavah, Mansur ;
Radzikowska, Elzbieta ;
Portincasa, Piero .
CELLS, 2020, 9 (04)
[3]   HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma [J].
Chen, Qi-tao ;
Zhang, Zhi-yuan ;
Huang, Qiao-ling ;
Chen, Hang-zi ;
Hong, Wen-bin ;
Lin, Tianwei ;
Zhao, Wen-xiu ;
Wang, Xiao-min ;
Ju, Cui-yu ;
Wu, Liu-zheng ;
Huang, Ya-ying ;
Hou, Pei-pei ;
Wang, Wei-jia ;
Zhou, Dawang ;
Deng, Xianming ;
Wu, Qiao .
NATURE METABOLISM, 2022, 4 (10) :1306-+
[4]   Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death [J].
Cheung, Eric C. ;
Ludwig, Robert L. ;
Vousden, Karen H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (50) :20491-20496
[5]   Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters [J].
Ciscato, Francesco ;
Ferrone, Lavinia ;
Masgras, Ionica ;
Laquatra, Claudio ;
Rasola, Andrea .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (09)
[6]   Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin [J].
DeWaal, Dannielle ;
Nogueira, Veronique ;
Terry, Alexander R. ;
Patra, Krushna C. ;
Jeon, Sang-Min ;
Guzman, Grace ;
Au, Jennifer ;
Long, Christopher P. ;
Antoniewicz, Maciek R. ;
Hay, Nissim .
NATURE COMMUNICATIONS, 2018, 9
[7]   Personalized risk assessment for dynamic transition of gastric neoplasms [J].
Fann, Jean Ching-Yuan ;
Chiang, Tsung-Hsien ;
Yen, Amy Ming-Fang ;
Lee, Yi-Chia ;
Wu, Ming-Shiang ;
Chen, Hsiu-Hsi .
JOURNAL OF BIOMEDICAL SCIENCE, 2018, 25
[8]   Helicobacter pylori infection induces stem cell-like properties in Correa cascade of gastric cancer [J].
He, JunJian ;
Hu, WeiChao ;
Ouyang, Qin ;
Zhang, ShengWei ;
He, LiJiao ;
Chen, WeiYan ;
Li, XinZhe .
CANCER LETTERS, 2022, 542
[9]   Studies on the Tissue Localization of HKDC1, a Putative Novel Fifth Hexokinase, in Humans [J].
Khan, Md. Wasim ;
Ding, Xianzhong ;
Cotler, Scott J. ;
Clarke, Michael ;
Layden, Brian T. .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2018, 66 (05) :385-392
[10]   Molecular mechanisms of epithelial-mesenchymal transition [J].
Lamouille, Samy ;
Xu, Jian ;
Derynck, Rik .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (03) :178-196
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