Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils.
Cancer Lett
; 592: 216903, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38670307
ABSTRACT
High levels of acetyl-CoA are considered a key metabolic feature of metastatic cancers. However, the impacts of acetyl-CoA metabolic accumulation on cancer microenvironment remodeling are poorly understood. In this study, using human hepatocellular carcinoma (HCC) tissues and orthotopic xenograft models, we found a close association between high acetyl-CoA levels in HCCs, increased infiltration of tumor-associated neutrophils (TANs) in the cancer microenvironment and HCC metastasis. Cytokine microarray and enzyme-linked immunosorbent assays (ELISA) revealed the crucial role of the chemokine (C-X-C motif) ligand 1(CXCL1). Mechanistically, acetyl-CoA accumulation induces H3 acetylation-dependent upregulation of CXCL1 gene expression. CXCL1 recruits TANs, leads to neutrophil extracellular traps (NETs) formation and promotes HCC metastasis. Collectively, our work linked the accumulation of acetyl-CoA in HCC cells and TANs infiltration, and revealed that the CXCL1-CXC receptor 2 (CXCR2)-TANs-NETs axis is a potential target for HCCs with high acetyl-CoA levels.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetyl Coenzyme A
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Carcinoma, Hepatocellular
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Chemokine CXCL1
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Tumor Microenvironment
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Liver Neoplasms
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Neutrophils
Limits:
Adult
/
Aged
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Cancer Lett
Year:
2024
Document type:
Article
Affiliation country:
China