{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang SF"],"funding":["Ministry of Science and Technology, Taiwan","Ministry of Education","Cheng Hsin General Hospital","National Chiao Tung University, from the Ministry of Education, Taiwan.","Taipei Veterans General Hospital, Taipei, Taiwan"],"pagination":["E3389"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6275069"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(11)"],"pubmed_abstract":["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 salubrina"],"journal":["International journal of molecular sciences"],"pubmed_title":["Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis."],"pmcid":["PMC6275069"],"funding_grant_id":["CY10605, CY10707","MOST 106-2320-B-010-032 and MOST 107-2320-B-010-044","V105A-018 and V106A-020","Aim for the Top University Plan","SPROUT Project- Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B)"],"pubmed_authors":["Wang SF","Lee HC","Chen MS","Yin PH","Chang YL","Chou YC","Wung CH","Yeh TS","Chen CF","Hung HH"],"additional_accession":[]},"is_claimable":false,"name":"Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis.","description":"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 salubrina","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2026-07-16T16:17:52.246Z","creation":"2019-03-27T00:11:39Z"},"accession":"S-EPMC6275069","cross_references":{"pubmed":["30380689"],"doi":["10.3390/ijms19113389"]}}