scholarly journals Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells

Aging ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 19660-19676 ◽  
Author(s):  
Yan Xu ◽  
Nanbin Liu ◽  
Yuhua Wei ◽  
Deren Zhou ◽  
Rui Lin ◽  
...  
Human Cell ◽  
2020 ◽  
Vol 33 (4) ◽  
pp. 1186-1196
Author(s):  
Yang Liu ◽  
Peng Qin ◽  
Rong Wu ◽  
Lianfang Du ◽  
Fan Li

Abstract Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial–mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.


2015 ◽  
Vol 13 (1) ◽  
pp. 237-242 ◽  
Author(s):  
YANLI YUAN ◽  
DEYU LI ◽  
HAIBO LI ◽  
LIANCAI WANG ◽  
GUANGJIN TIAN ◽  
...  

2011 ◽  
Vol 286 (12) ◽  
pp. 10495-10504 ◽  
Author(s):  
Mario A. Shields ◽  
Surabhi Dangi-Garimella ◽  
Seth B. Krantz ◽  
David J. Bentrem ◽  
Hidayatullah G. Munshi

Pancreatic ductal adenocarcinoma (PDAC) is characterized by pronounced fibrotic reaction composed primarily of type I collagen. Although type I collagen functions as a barrier to invasion, pancreatic cancer cells have been shown to respond to type I collagen by becoming more motile and invasive. Because epithelial-mesenchymal transition is also associated with cancer invasion, we examined the extent to which collagen modulated the expression of Snail, a well known regulator of epithelial-mesenchymal transition. Relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels induced Snail. Inhibiting the activity or expression of the TGF-β type I receptor abrogated collagen-induced Snail. Downstream of the receptor, we showed that Smad3 and Smad4 were critical for the induction of Snail by collagen. In contrast, Smad2 or ERK1/2 was not involved in collagen-mediated Snail expression. Overexpression of Snail in PDAC cells resulted in a robust membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14)-dependent invasion through collagen-coated transwell chambers. Snail-expressing PDAC cells also demonstrated MT1-MMP-dependent scattering in three-dimensional collagen gels. Mechanistically, Snail increased the expression of MT1-MMP through activation of ERK-MAPK signaling, and inhibiting ERK signaling in Snail-expressing cells blocked two-dimensional collagen invasion and attenuated scattering in three-dimensional collagen. To provide in vivo support for our findings that Snail can regulate MT1-MMP, we examined the expression of Snail and MT1-MMP in human PDAC tumors and found a statistically significant positive correlation between MT1-MMP and Snail in these tumors. Overall, our data demonstrate that pancreatic cancer cells increase Snail on encountering collagen-rich milieu and suggest that the desmoplastic reaction actively contributes to PDAC progression.


2013 ◽  
Vol 104 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Ayano Kabashima-Niibe ◽  
Hajime Higuchi ◽  
Hiromasa Takaishi ◽  
Yohei Masugi ◽  
Yumi Matsuzaki ◽  
...  

2013 ◽  
Vol 228 (6) ◽  
pp. 1255-1263 ◽  
Author(s):  
Shin Hamada ◽  
Kennichi Satoh ◽  
Shin Miura ◽  
Morihisa Hirota ◽  
Atsushi Kanno ◽  
...  

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