LPA(1/3) signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer

doi:10.1016/j.bbalip.2018.07.005

CNU IR > Pharmacy and Science > Dept. of Cosmetic Science and institute of cosmetic science > Periodical Articles > Item 310902800/32194

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

Title:	LPA(1/3) signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer
Authors:	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
Contributors:	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
Keywords:	LPA VEGF-C Prostate cancer CRT eIF2 alpha Lymphangiogenesis
Date:	2018-10
Issue Date:	2019-11-15 15:44:42 (UTC+8)
Publisher:	ELSEVIER SCIENCE BV
Abstract:	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.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.1016/j.bbalip.2018.07.005
Relation:	Separation and Purification Technology, v.1863, n.10, pp.1305-1315
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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