Periostin secreted from podoplanin-positive cancer-associated fibroblasts promotes metastasis of gastric cancer by regulating cancer stem cells via AKT and YAP signaling pathway.
Mol Carcinog
; 62(5): 685-699, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36785937
ABSTRACT
Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells present in the tumor microenvironment (TME), which play a critical role in gastric cancer (GC) progression. Here, we examined a subset of CAFs with high podoplanin (PDPN) expression, which is correlated with tumor metastasis and poor survival in GC patients. Animal models of gastric cancer liver metastasis monitored by micro-PET/CT confirmed that periostin (POSTN) derived from PDPN(+) CAFs regulated CAFs' pro-migratory ability. Mechanistically, PDPN(+) CAFs secreted POSTN to modulate cancer stem cells (CSCs) through FAK/AKT phosphorylation. Furthermore, POSTN could also activate FAK/YAP signaling in GC cells to produce increased amounts of IL-6, which in turn induced phosphorylation of PI3K/AKT in PDPN(+) CAFs. Prolonged PI3K/AKT pathway activation in PDPN(+) CAFs maintains the production of POSTN and the effect on CSC enrichment and GC cell migration. In conclusion, our study demonstrated a positive feedback loop between PDPN(+) CAFs and CSCs during GC progression and suggested a selective target for GC treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Fibroblastos Associados a Câncer
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Carcinog
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China