Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates caspases in human prostate cancer cells through sigma 1 receptor

Biochemical and Biophysical Research Communications
Dibash DasMoira Sauane

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapy is currently evaluated in clinical studies as a tumor cell-selective pro-apoptotic approach. Unfortunately, many clinical studies have shown that cancer cells acquire TRAIL resistance and finally avoid TRAIL-induced apoptosis. Therefore, defining the mechanisms that permit TRAIL to activate apoptosis is critical for the development of strategies that maximize the potential effectiveness of TRAIL in clinical applications. This study aims at understanding the molecular mechanisms underlying TRAIL-induced apoptosis and unraveling signaling pathways that could revert sensitivity to apoptosis stimuli. Our current study demonstrates for the first time that Sigma 1 Receptor (Sig1R), a ligand-regulated protein chaperone, contributes to TRAIL induction of apoptosis. We show that Sig1R agonist (+)-SKF10047 action or increasing Sig1R expression, significantly reduced apoptosis by TRAIL in prostate cell lines, indicating the importance of Sig1R and signifying that higher levels of Sig1R in prostate cancer cells make them more resistant to TRAIL treatment. Here we show that Sig1R is critically involved in TRAIL-induced caspase activation. Furthermore, we show that...Continue Reading

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Citations

Jun 9, 2016·International Journal of Molecular Sciences·Leah PersaudMoira Sauane
Mar 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mathias KranzJens Pietzsch
Aug 26, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Markos-Orestis GeorgiadisIoannis Papanastasiou
Sep 9, 2017·Oxidative Medicine and Cellular Longevity·Tzu-Yu WengShang-Yi A Tsai
Aug 24, 2021·Veterinary and Comparative Oncology·Soo-Hyeon KimJung-Hyang Sur

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