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Sphingosine 1‐phosphate‐induced autophagy is mediated through activating endoplasmic reticulum stress response in human prostate cancer PC‐3 cells
Author(s) -
Shih ChihJen,
Huang YuanLi,
Chang ChiLun,
Huang WeiPang,
Lee Hsinyu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.954.9
Subject(s) - autophagy , endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , gene knockdown , sphingosine 1 phosphate , chemistry , pi3k/akt/mtor pathway , g protein coupled receptor , sphingosine , receptor , signal transduction , biology , apoptosis , biochemistry
Sphingosine 1‐phosphate (S1P) is a bioactive lysophospholipid that binds to a family of G protein‐coupled receptors (GPCRs), termed S1P 1 ~S1P 5 . Our previous study has reported that S1P inhibits PC‐3, a human prostate cancer cell, proliferation through activation of autophagy. In addition, S1P‐induced autophagy plays a prosurvival role in PC‐3 cells. Accumulating evidences have studied that the cytoprotective effect of autophagy can be triggered by ER stress induction. Thus, we attempted to investigate whether S1P‐induced autophagy is resulted from triggering ER stress in PC‐3 cells. By monitoring XBP‐1 mRNA splicing, a characteristics of ER stress, we demonstrated that S1P triggers ER stress in a concentration and a time‐dependent manner. In addition, we also showed that S1P 1 and S1P 5 are 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 significantly abolished S1P‐induced autophagy. In summary, our results demonstrated for the first time that S1P‐triggered ER stress is responsible for autophagy in PC‐3 cells. Support by: Institute of Zoology