Back to Search Start Over

Hexokinase 2 nonmetabolic function‐mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression.

Authors :
Tong, Yingying
Liu, Xin
Wu, Lihui
Xiang, Yaoxian
Wang, Jing
Cheng, Yurong
Zhang, Chan
Han, Baojuan
Wang, Li
Yan, Dong
Source :
Cancer Science; Aug2024, Vol. 115 Issue 8, p2673-2685, 13p
Publication Year :
2024

Abstract

Aberrant signaling in tumor cells induces nonmetabolic functions of some metabolic enzymes in many cellular activities. As a key glycolytic enzyme, the nonmetabolic function of hexokinase 2 (HK2) plays a role in tumor immune evasion. However, whether HK2, dependent of its nonmetabolic activity, plays a role in human pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains unclear. Here, we demonstrated that HK2 acts as a protein kinase and phosphorylates IκBα at T291 in PDAC cells, activating NF‐κB, which enters the nucleus and promotes the expression of downstream targets under hypoxia. HK2 nonmetabolic activity‐promoted activation of NF‐κB promotes the proliferation, migration, and invasion of PDAC cells. These findings provide new insights into the multifaceted roles of HK2 in tumor development and underscore the potential of targeting HK2 protein kinase activity for PDAC treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13479032
Volume :
115
Issue :
8
Database :
Complementary Index
Journal :
Cancer Science
Publication Type :
Academic Journal
Accession number :
178910020
Full Text :
https://doi.org/10.1111/cas.16204