Autor: |
Jichun Lin, Wenshuo Fang, Zhuo Xiang, Qingqing Wang, Huapeng Cheng, Shimin Chen, Jing Fang, Jia Liu, Qiang Wang, Zhimin Lu, Leina Ma |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
Frontiers in Immunology, Vol 14 (2023) |
Druh dokumentu: |
article |
ISSN: |
1664-3224 |
DOI: |
10.3389/fimmu.2023.1189953 |
Popis: |
Immune therapies targeting the PD-1/PD-L1 pathway have been employed in the treatment of breast cancer, which requires aerobic glycolysis to sustain breast cancer cells growth. However, whether PD-L1 expression is regulated by glycolysis in breast cancer cells remains to be further elucidated. Here, we demonstrate that glycolytic enzyme hexokinase 2 (HK2) plays a crucial role in upregulating PD-L1 expression. Under high glucose conditions, HK2 acts as a protein kinase and phosphorylates IκBα at T291 in breast cancer cells, leading to the rapid degradation of IκBα and activation of NF-κB, which enters the nucleus and promotes PD-L1 expression. Immunohistochemistry staining of human breast cancer specimens and bioinformatics analyses reveals a positive correlation between HK2 and PD-L1 expression levels, which are inversely correlated with immune cell infiltration and survival time of breast cancer patients. These findings uncover the intrinsic and instrumental connection between aerobic glycolysis and PD-L1 expression-mediated tumor cell immune evasion and underscore the potential to target the protein kinase activity of HK2 for breast cancer treatment. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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