Notch signaling regulates vasculogenic mimicry and promotes cell morphogenesis and the epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma
1
Issued Date
2022-12-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85144526674
Pubmed ID
36548277
Journal Title
PLoS ONE
Volume
17
Issue
12 December
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.17 No.12 December (2022)
Suggested Citation
Benjakul N., Prakobphol N., Tangshewinsirikul C., Dulyaphat W., Svasti J., Charngkaew K., Kangsamaksin T. Notch signaling regulates vasculogenic mimicry and promotes cell morphogenesis and the epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma. PLoS ONE Vol.17 No.12 December (2022). doi:10.1371/journal.pone.0279001 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86359
Title
Notch signaling regulates vasculogenic mimicry and promotes cell morphogenesis and the epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma
Author's Affiliation
Other Contributor(s)
Abstract
Vasculogenic mimicry (VM) is the process where cancer cells adopt endothelial characteristics by forming tube-like structures and perfusing channels. This phenomenon has been demonstrated in several types of solid tumors and associated with the growth and survival of tumor cells. In this study, we investigated the presence of VM formation in human pancreatic ductal adenocarcinoma (PDAC) and elucidated the molecular mechanisms underlying the VM process. In human PDAC tissues, CD31-negative, periodic acid-Schiff (PAS)-positive channels were predominantly found in desmoplastic areas, which are generally also hypovascularized. We found a positive correlation of VM capacity to tumor size and NOTCH1 expression and nuclear localization with statistical significance, implicating that Notch activity is involved with VM formation. Additionally, our data showed that the presence of growth or angiogenic factors significantly increased Notch activity in PDAC cell lines and upregulated several mesenchymal marker genes, such as TWIST1 and SNAI1, which can be inhibited by a gamma-secretase inhibitor. Our data showed that Notch signaling plays an important role in inducing VM formation in PDAC by promoting the epithelial-to-mesenchymal transition process.