scholarly journals The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Song Zhao ◽  
Hongdan Li ◽  
Qingjun Wang ◽  
Chang Su ◽  
Guan Wang ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiu-Xiu Zhang ◽  
Hong-Dan Li ◽  
Song Zhao ◽  
Liang Zhao ◽  
Hui-Juan Song ◽  
...  

Invasion is a major characteristic of hepatocellular carcinoma and one of the main causes of refractory to treatment. We have previously reported that GRP78 promotes the invasion of hepatocellular carcinoma although the mechanism underlying this change remains uncertain. In this paper, we explored the role of the cell surface GRP78 in the regulation of cancer cell invasion in hepatocellular carcinoma cells. We found that neutralization of the endogenous cell surface GRP78 with the anti-GRP78 antibody inhibited the adhesion and invasion in hepatocellular carcinoma cell lines Mahlavu and SMMC7721. However, forced expression of the cell surface GRP78 facilitated the adhesion and invasion in SMMC7721. We further demonstrated that inhibition of the endogenous cell surface GRP78 specifically inhibited the secretion and activity of MMP-2 but did not affect the secretion and activity of MMP-9. We also found that inhibition of the cell surface GRP78 increased E-Cadherin expression and decreased N-Cadherin level. On the contrary, forced expression of the cell surface GRP78 increased N-Cadherin expression and decreased E-Cadherin level, suggesting that the cell surface GRP78 plays critical role in the regulation of EMT process. These findings suggest that the cell surface GRP78 plays a stimulatory role in the invasion process and may be a potential anti-invasion target for the treatment of hepatocellular carcinoma.


2016 ◽  
Vol 24 (36) ◽  
pp. 4788
Author(s):  
Guo-Zhan Jia ◽  
Yu-Long Zhai ◽  
Shuai Zhou ◽  
Bo Zhang ◽  
Tao Wu ◽  
...  

Biochemistry ◽  
2018 ◽  
Vol 57 (7) ◽  
pp. 1201-1211 ◽  
Author(s):  
Ahmad Saad ◽  
Benjamin Liet ◽  
Gilles Joucla ◽  
Xavier Santarelli ◽  
Justine Charpentier ◽  
...  

FEBS Letters ◽  
2016 ◽  
Vol 590 (16) ◽  
pp. 2700-2708 ◽  
Author(s):  
Maaged A. Akiel ◽  
Prasanna K. Santhekadur ◽  
Rachel G. Mendoza ◽  
Ayesha Siddiq ◽  
Paul B. Fisher ◽  
...  

2015 ◽  
Vol 35 (6) ◽  
pp. 2333-2348 ◽  
Author(s):  
Liang Shi ◽  
Lili Wu ◽  
Zhanguo Chen ◽  
Jianrong Yang ◽  
Xiaofei Chen ◽  
...  

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. A major cause for the failure of cancer therapy is the development of chemoresistance. Although progress has been made in the study of the mechanisms underlying cancer cells resistance, little is known about the role of microRNAs (miRNAs) in cancer therapy resistance. Methods and Results: Fifteen miRNAs, including 6 up-regulated miRNAs (> 2.0-fold) and 9 down-regulated miRNAs (< 0.5-fold) were differentially expressed in 5-fluorouracil-resistant and their parental cell-lines (HepG2, HepG2/5-FU) by miRNA microarrays. Microarray results were confirmed by validating quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Up-regulation of miR-141 expression resulted in a significant inhibition of 5-FU-mediated cytotoxicity and apoptosis in various hepatocellular carcinoma cells-lines. Mechanically, miR-141 promoted Kelch-like ECH-associated protein 1 (Keap1) mRNA degradation by directly targeting the Keap1 3'untranslated region (3'UTR). Treatment with miR-141 mimics in parental HepG2 cells, restored miR-141 expression and reduced Keap1 levels, thereby resulting in erythroid transcription factor NFE2-L2 (Nrf2) nuclear translocation, activation of Nrf2-dependent HO-1 gene transcription, and subsequent enhancement in 5-FU resistance. Conversely, restoring the expression of Keap1 partly recovered 5-FU sensitivity by counteracting miR-141-mediated 5-FU resistance. Conclusion: Our study showed that miR-141 plays a key role in 5-FU resistance by down-regulating Keap1 expression, thereby reactivating the Nrf2-dependent antioxidant pathway, which may serve as a potential target for overcoming 5-FU resistance in hepatocellular carcinoma cells.


Sign in / Sign up

Export Citation Format

Share Document