title: Extrinsic sphingosine 1-phosphate activates S1P5 and induces autophagy through generating endoplasmic reticulum stress in human prostate cancer PC-3 cells.
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.
authors: Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan, ROC; Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan.
authors: Yuan-Li
authors: YL
authors: Huang
authors: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors: Chi-Lun
authors: CL
authors: Chang
authors: Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan.
authors: Chih-Hsin
authors: CH
authors: Tang
authors: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors: Yueh-Chien
authors: YC
authors: Lin
authors: Instrumentation Center, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC; Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors: Tsai-Kai
authors: TK
authors: Ju
authors: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC; Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: wphuang@ntu.edu.tw.
authors: Wei-Pang
authors: WP
authors: Huang
authors: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC; Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC; Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC; Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan, ROC; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: hsinyu@ntu.edu.tw.
authors: Hsinyu
authors: H
authors: Lee
mesh_terms: D001343:Autophagy / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms; D034622:RNA Interference; D012326:RNA Splicing / Q000235:genetics; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics*; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007295:Inositol Phosphates; D008246:Lysophospholipids; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D049349:Receptors, Lysosphingolipid; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C060506:sphingosine 1-phosphate; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D013110:Sphingosine; D002118:Calcium
keywords: Autophagy; ER stress; Prostate cancer; Sphingosine 1-phosphate