Cancer-associated fibroblasts drive early pancreatic cancer cell invasion via the SOX4/MMP11 signalling axis.
Biochim Biophys Acta Mol Basis Dis
; 1870(1): 166852, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37633471
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant cancer-associated fibroblasts (CAFs), early perineural invasion (PNI) and microvascular invasion (MVI). However, the differentiation trajectories and underlying molecular mechanisms of CAFs in PDAC early invasion have not been fully elucidated. In this study, we integrated and reanalysed single-cell data from the National Geoscience Data Centre (NGDC) database and confirmed that myofibroblast-like CAFs (myCAFs) mediated epithelial-mesenchymal transformation (EMT) and enhanced the invasion abilities of PDAC cells by secreting regulators of angiogenesis and metastasis. Furthermore, we constructed a differentiation trajectory of CAFs and revealed that reprogramming from iCAFs to myCAFs was associated with poor prognosis. Mechanistically, SOX4 was aberrantly activated in myCAFs, which promoted the secretion of MMP11 and eventually induced early cancer cell invasion. Together, our results provide a comprehensive transcriptomic overview of PDAC patients with early invasion and reveal the intercellular crosstalk between myCAFs and cancer cells, which suggests potential targets for early invasion PDAC therapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Carcinoma Ductal Pancreático
/
Fibroblastos Associados a Câncer
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article