scholarly journals Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway

Oncotarget ◽  
2016 ◽  
Vol 7 (45) ◽  
pp. 74132-74151 ◽  
Author(s):  
Sheng-Fan Wang ◽  
Meng-Shian Chen ◽  
Yueh-Ching Chou ◽  
Yune-Fang Ueng ◽  
Pen-Hui Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals MiR-99a and MiR-491 Regulate Cisplatin Resistance in Human Gastric Cancer Cells by Targeting CAPNS1

2016 ◽  
Vol 12 (12) ◽  
pp. 1437-1447 ◽  
Author(s):  
Yajie Zhang ◽  
Wenxia Xu ◽  
Pan Ni ◽  
Aiping Li ◽  
Jianwei Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis

2018 ◽  
Vol 19 (11) ◽  
pp. 3389 ◽  
Author(s):  
Sheng-Fan Wang ◽  
Chih-Hsuan Wung ◽  
Meng-Shian Chen ◽  
Chian-Feng Chen ◽  
Pen-Hui Yin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Stress Response ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Translation Initiation Factor ◽  
Heme Oxygenase 1 ◽  
Human Gastric Cancer ◽  
Integrated Stress Response ◽  
Gastric Cancer Cells

The integrated stress response (ISR) pathway is essential for adaption of various stresses and is related to mitochondrion-to-nucleus communication. Mitochondrial dysfunction-induced reactive oxygen species (ROS) was demonstrated to activate general control nonderepressible 2 (GCN2)–eukaryotic translation initiation factor 2α (eIF2α)–activating transcription factor-4 (ATF4) pathway-mediated cisplatin resistance of human gastric cancer cells. However, whether or how ISR activation per se could enhance chemoresistance remains unclear. In this study, we used eIF2α phosphatase inhibitor salubrinal to activate the ISR pathway and found that salubrinal reduced susceptibility to cisplatin. Moreover, salubrinal up-regulated ATF4-modulated gene expression, and knockdown of ATF4 attenuated salubrinal-induced drug resistance, suggesting that ATF4-modulated genes contribute to the process. The ATF4-modulated genes, xCT (a cystine/glutamate anti-transporter), tribbles-related protein 3 (TRB3), heme oxygenase 1 (HO-1), and phosphoenolpyruvate carboxykinase 2 (PCK2), were associated with a poorer prognosis for gastric cancer patients. By silencing individual genes, we found that xCT, but not TRB3, HO-1, or PCK2, is responsible for salubrinal-induced cisplatin resistance. In addition, salubrinal increased intracellular glutathione (GSH) and decreased cisplatin-induced lipid peroxidation. Salubrinal-induced cisplatin resistance was attenuated by inhibition of xCT and GSH biosynthesis. In conclusion, our results suggest that ISR activation by salubrinal up-regulates ATF4-modulated gene expression, increases GSH synthesis, and decreases cisplatin-induced oxidative damage, which contribute to cisplatin resistance in gastric cancer cells.

MiR-129 regulates cisplatin-resistance in human gastric cancer cells by targeting P-gp

2017 ◽  
Vol 86 ◽  
pp. 450-456 ◽  
Author(s):  
Chaojing Lu ◽  
Zhengxiang Shan ◽  
Chunguang Li ◽  
Lixin Yang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals The long noncoding RNA CRAL reverses cisplatin resistance via the miR-505/CYLD/AKT axis in human gastric cancer cells

RNA Biology ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. 1576-1589 ◽  
Author(s):  
Zhangding Wang ◽  
Qiang Wang ◽  
Guifang Xu ◽  
Na Meng ◽  
Xinli Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals JWA reverses cisplatin resistance via the CK2—XRCC1 pathway in human gastric cancer cells

2014 ◽  
Vol 5 (12) ◽  
pp. e1551-e1551 ◽  
Author(s):  
W Xu ◽  
Q Chen ◽  
Q Wang ◽  
Y Sun ◽  
S Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals MicroRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells

2017 ◽  
Vol 38 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Tao Jiang ◽  
Pengfei Dong ◽  
Long Li ◽  
Xiao Ma ◽  
Pei Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells
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