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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/32194

    標題: LPA(1/3) signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer
    作者: Lin, Yueh-Chien
    Chen, Chien-Chin
    Chen, Wei-Min
    Lu, Kuan-Ying
    Shen, Tang-Long
    Jou, Yeong-Chin
    Shen, Cheng-Huang
    Ohbayashi, Norihiko
    Kanaho, Yasunori
    Huang, Yuan-Li
    Lee, Hsinyu
    貢獻者: Natl Taiwan Univ, Dept Life Sci
    Univ Tsukuba, Fac Med, Dept Physiol Chem
    Univ Tsukuba, Grad Sch Comprehens Human Sci
    Chia Yi Christian Hosp, Dept Pathol
    Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
    Natl Taiwan Univ, Dept Plant Pathol & Microbiol
    Chia Yi Christian Hosp, Dept Urol
    Asia Univ, Dept Biotechnol
    China Med Univ, China Med Univ Hosp, Dept Med Res
    Natl Taiwan Univ, Dept Elect Engn
    Natl Taiwan Univ, Inst Biomed Elect & Bioinformat
    Natl Taiwan Univ, Ctr Biotechnol
    關鍵字: LPA
    Prostate cancer
    eIF2 alpha
    日期: 2018-10
    上傳時間: 2019-11-15 15:44:42 (UTC+8)
    摘要: Lysophosphatidic acid (LPA) is a bioactive lipid growth factor which is present in high levels in serum and platelets. LPA binds to its specific G-protein-coupled receptors, including LPA(1) to LPA(6), thereby regulating various physiological functions, including cancer growth, angiogenesis, and lymphangiogenesis. Our previous study showed that LPA promotes the expression of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C in prostate cancer (PCa) cells. Interestingly, LPA has been shown to regulate the expression of calreticulin (CRT), a multifunctional chaperone protein, but the roles of CRT in PCa progression remain unclear. Here we investigated the involvement of CRT in LPA-mediated VEGF-C expression and lymphangiogenesis in PCa. Knockdown of CRT significantly reduced LPA-induced VEGF-C expression in PC-3 cells. Moreover, LPA promoted CRT expression through LPA receptors LPA(1) and LPA(3), reactive oxygen species (ROS) production, and phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha). Tumor-xenografted mouse experiments further showed that CRT knockdown suppressed tumor growth and lymphangiogenesis. Notably, clinical evidence indicated that the LPA-producing enzyme autotaxin (ATX) is related to CRT and that CRT level is highly associated with lymphatic vessel density and VEGF-C expression. Interestingly, the pharmacological antagonist of LPA receptors significantly reduced the lymphatic vessel density in tumor and lymph node metastasis in tumor-bearing nude mice. Together, our results demonstrated that CRT is critical in PCa progression through the mediation of LPA-induced VEGF-C expression, implying that targeting the LPA signaling axis is a potential therapeutic strategy for PCa.
    link: http://dx.doi.org/10.1016/j.bbalip.2018.07.005
    關聯: Separation and Purification Technology, v.1863, n.10, pp.1305-1315
    Appears in Collections:[化妝品應用與管理系(所)] 期刊論文

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