LPA <subscript>1/3</subscript> signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer.
In: Biochimica et biophysica acta. Molecular and cell biology of lipids, Jg. 1863 (2018-10-01), Heft 10, S. 1305-1315
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Zugriff:
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 2α (eIF2α). 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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Titel: |
LPA <subscript>1/3</subscript> signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer.
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Autor/in / Beteiligte Person: | Lin, YC ; Chen, CC ; Chen, WM ; Lu, KY ; Shen, TL ; Jou, YC ; Shen, CH ; Ohbayashi, N ; Kanaho, Y ; Huang, YL ; Lee, H |
Zeitschrift: | Biochimica et biophysica acta. Molecular and cell biology of lipids, Jg. 1863 (2018-10-01), Heft 10, S. 1305-1315 |
Veröffentlichung: | Amsterdam : Elsevier, 2018 |
Medientyp: | academicJournal |
ISSN: | 1879-2618 (electronic) |
DOI: | 10.1016/j.bbalip.2018.07.005 |
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