Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer.
Journal
Signal transduction and targeted therapy
ISSN: 2059-3635
Titre abrégé: Signal Transduct Target Ther
Pays: England
ID NLM: 101676423
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
21
06
2020
accepted:
21
09
2020
revised:
31
08
2020
entrez:
30
10
2020
pubmed:
31
10
2020
medline:
14
10
2021
Statut:
epublish
Résumé
Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma (PDAC). Therapeutics that target the driver mutations, especially the KRAS oncoprotein and its effector cascades, have been ineffective. It is increasing clear that the extensive fibro-inflammatory stroma (or desmoplasia) of PDAC plays an active role in the progression and therapeutic resistance of PDAC. The desmoplastic stroma is composed of dense extracellular matrix (ECM) deposited mainly by the cancer-associated-fibroblasts (CAFs) and infiltrated with various types of immune cells. The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells. In addition, mounting evidence have demonstrated that both CAFs and ECM promote PDAC cells aggressiveness through multiple mechanisms, particularly engagement of the epithelial-mesenchymal transition (EMT) program. Acquisition of a mesenchymal-like phenotype renders PDAC cells more invasive and resistant to therapy-induced apoptosis. Here, we critically review seminal and recent articles on the signaling mechanisms by which each stromal element promotes EMT in PDAC. We discussed the experimental models that are currently employed and best suited to study EMT in PDAC, which are instrumental in increasing the chance of successful clinical translation.
Identifiants
pubmed: 33122631
doi: 10.1038/s41392-020-00341-1
pii: 10.1038/s41392-020-00341-1
pmc: PMC7596088
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
249Subventions
Organisme : NCI NIH HHS
ID : P50 CA196510
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223112
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA219697
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224083
Pays : United States
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