Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment.
|
| Abstract |
Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.
|
|---|---|
| Authors | Jiali Qian, Chuxin Huang, Mimi Wang, Ying Liu, Yingying Zhao, Miao Li, Xi Zhang, Xiangyu Gao, Yawen Zhang, Yi Wang, Jinya Huang, Jiajun Li, Qiwen Zhou, Rui Liu, Xuanchun Wang, Jiefeng Cui, Yehong Yang |
| Journal | Redox biology (Redox Biol) Vol. 71 Pg. 103103 (May 2024) ISSN: 2213-2317 [Electronic] Netherlands |
| PMID | 38471282 (Publication Type: Journal Article) |
| Copyright | Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!