Tumour cell-derived serglycin promotes IL-8 secretion of CAFs in gastric cancer.
Br J Cancer
; 131(2): 271-282, 2024 Jul.
Article
de En
| MEDLINE
| ID: mdl-38862740
ABSTRACT
BACKGROUND:
Cancer-associated fibroblasts (CAFs)-derived IL-8 plays important roles in chemoresistance, immunosuppression, and lymph node metastasis of gastric cancer. However, the mechanisms underlying IL-8 production in CAFs remains unclear.METHODS:
DNA pulldown assay was performed to identify the transcription factors responsible for IL-8 expression in CAFs, which was further verified using CHIP-qPCR and DNA agarose gel electrophoresis assays. The cellular localisation of IL-8 was analysed using multiplex immunofluorescence (MxIF).RESULTS:
MxIF demonstrated that IL-8 was mainly produced by CAFs in gastric cancer. Lysine[K]-specific demethylase 5B (KDM5B) was identified as an IL-8 transcription factor in CAFs, and the binding of KDM5B to phosphorylated RB1 limited the transcriptional regulation of IL-8 in gastric cancer cells. Serglycin (SRGN) secreted by tumour cells activated the CD44/c-Myc pathway to upregulate KDM5B expression, thereby promoting IL-8 production in CAFs. Furthermore, tumour-associated neutrophils (TANs)-derived regenerating family member 4 (REG4) upregulates SRGN expression by activating cAMP-responsive element binding protein 1 (CREB1) in gastric cancer cells. Thus, the SRGN-IL-8-TANs-SRGN loop, which facilitates tumour progression, has been explored in gastric cancer.CONCLUSIONS:
This study revealed the mechanisms of the preferential production of IL-8 by CAFs in gastric cancer, and paves the way for potential new therapeutic strategies for gastric cancer.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéoglycanes
/
Tumeurs de l'estomac
/
Interleukine-8
/
Protéines du transport vésiculaire
/
Fibroblastes associés au cancer
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Br J Cancer
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine