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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Up-regulation of gamma-synuclein contributes to cancer cell survival under endoplasmic reticulum stress
1Division of Signal Transduction and Molecular Targeting Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Abstract:
Previous studies have demonstrated that gamma-synuclein is overexpressed in a variety of human malignancies. Overexpression of gamma-synuclein in human breast cancer cells leads to an increase in cell motility, resistance to chemotherapeutic drugs, and mitotic checkpoint dysfunction. We report in this study that gamma-synuclein is up-regulated by endoplasmic reticulum stress. The up-regulation of gamma-synuclein expression by endoplasmic reticulum stress is mediated, at least in part, by activation transcription factor (ATF) 4. Knockdown of gamma-synuclein sensitized human breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Induction of apoptosis by endoplasmic reticulum stress when gamma-synuclein was inhibited was dependent on JNK or caspase activation, with caspase-3 and caspase-7 being involved. Treatment with the JNK or caspase-3 and caspase-7 inhibitor partially blocked endoplasmic reticulum stress-induced apoptosis in breast cancer cells transfected with or without the siRNA against gamma-synuclein. Taken together, these data suggest that gamma-synuclein may promote cancer progression by suppressing endoplasmic reticulum stress-induced apoptosis.
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