Extrinsic sphingosine 1-phosphate activates S1P5 and induces autophagy through generating endoplasmic reticulum stress in human prostate cancer PC-3 cells
Journal
Cellular Signalling
Journal Volume
26
Journal Issue
3
Pages
611-618
Date Issued
2014
Author(s)
Huang, Y.-L.
Chang, C.-L.
Tang, C.-H.
Lin, Y.-C.
Ju, T.-K.
Huang, W.-P.
Lee, H.
Abstract
Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that binds to a family of G protein-coupled receptors (GPCRs), termed S1P1-S1P5. Our previous study has reported that S1P induces autophagy in human prostate cancer PC-3 cell. In addition, S1P-induced autophagy plays a prosurvival role in PC-3 cells. Accumulating evidence has shown that the autophagy responses triggered by ER stress signaling have cytoprotective effects. Thus, we attempted to investigate whether S1P-induced autophagy is a result of triggering ER stress in PC-3 cells. By monitoring XBP-1 mRNA splicing, a characteristic of ER stress, we demonstrate that S1P triggers ER stress in a concentration-dependent and time-dependent manner. Moreover, DiH S1P, a membrane-nonpermeable S1P analog without intracellular effects also enhances ER stress. Meanwhile, we also show that S1P5 is required for S1P-induced ER stress by using RNA interference experiments. Furthermore, signaling analyses revealed that PI3K, PLC, and ROS production were involved in S1P's effects on ER stress induction. On the other hand, knockdown of XBP-1 abolished S1P-induced autophagy. In summary, our results demonstrate for the first time that the extracellular S1P-triggered ER stress is responsible for autophagy induction in PC-3 cells. ? 2013 Elsevier Inc.
Subjects
Autophagy; ER stress; Prostate cancer; Sphingosine 1-phosphate
SDGs
Other Subjects
activating transcription factor 6; initiation factor 2alpha; messenger RNA; phosphatidylinositol 3 kinase; phospholipase C; protein kinase B; reactive oxygen metabolite; small interfering RNA; sphingosine 1 phosphate; sphingosine 1 phosphate receptor; sphingosine 1 phosphate receptor 5; unclassified drug; X box binding protein 1; article; autophagy; cancer cell; cell protection; cell survival; concentration (parameters); controlled study; endoplasmic reticulum stress; gene expression regulation; gene silencing; human; human cell; intracellular signaling; male; molecular dynamics; priority journal; prostate cancer; protein cleavage; protein expression; protein phosphorylation; RNA interference; RNA splicing; upregulation; Autophagy; ER stress; Prostate cancer; Sphingosine 1-phosphate; Autophagy; Calcium; Cell Line, Tumor; DNA-Binding Proteins; Endoplasmic Reticulum Stress; Humans; Inositol Phosphates; Lysophospholipids; Male; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Reactive Oxygen Species; Receptors, Lysosphingolipid; RNA Interference; RNA Splicing; RNA, Small Interfering; Signal Transduction; Sphingosine; Transcription Factors; Type C Phospholipases
Type
journal article