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

Authors :
Fang, Ziqing
Zhang, Weitong
Wang, Huizhen
Zhang, Chaoyang
Li, Jing
Chen, Wanjing
Xu, Xin
Wang, Luyang
Ma, Mengdi
Zhang, Shangxin
Li, Yongxiang
Source :
Cellular & Molecular Life Sciences. 11/15/2024, Vol. 81 Issue 1, p1-17. 17p.
Publication Year :
2024

Abstract

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-β1 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-β1 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1420682X
Volume :
81
Issue :
1
Database :
Academic Search Index
Journal :
Cellular & Molecular Life Sciences
Publication Type :
Academic Journal
Accession number :
180932448
Full Text :
https://doi.org/10.1007/s00018-024-05491-x