LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110β.
LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110β.
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LPAR5 通过激活 IA 类 PI3K 催化亚基 p110β 促进甲状腺癌细胞增殖和迁移
DOI：
10.1111/cas.14837
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发表时间：
2021-04
期刊：
影响因子：
5.7
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Zhao WJ;Zhu LL;Yang WQ;Xu SJ;Chen J;Ding XF;Liang Y;Chen G
溶血磷脂酸受体5（LPAR 5）参与介导甲状腺癌的进展，但其潜在机制需要进一步揭示。在这项研究中，我们通过分析癌症基因组图谱（TCGA）数据库和在人甲状腺癌组织中进行免疫组织化学测定，证实了LPAR 5在甲状腺乳头状癌（PTC）中上调，特别是在BRAF样PTC中。LPAR 5特异性拮抗剂TC LPA 5 4处理显著抑制CGTH-W3、TPC-1、B-CPAP和BHT-101细胞增殖以及CGTH-W3和TPC-1细胞迁移。在体内，TC LPA 5 4处理可以延迟裸鼠中CGTH-W3异种移植物的生长。我们还发现，在CGTH-W3和TPC-1细胞中，LPA 5特异性拮抗剂TC LPA 5 4、PI 3 K抑制剂渥曼青霉素或mTOR抑制剂雷帕霉素预处理消除了LPA刺激的Akt和p70 S6 K1的磷酸化。用LPA刺激转染pEGFPC 1-Grp 1-PH融合蛋白的CGTH-W3细胞导致磷脂酰肌醇（3，4，5）-三磷酸的产生，这表明PI 3 K被LPA直接激活。用p110β-siRNA代替p110α-siRNA转染抑制了LPA刺激的Akt和S6 K1磷酸化水平的升高。免疫沉淀实验进一步证实了LPAR 5与p110β之间存在相互作用。总之，我们提供了新的见解，即下调LPAR 5通过PI 3 K/Akt途径降低增殖和迁移表型。抑制LPAR 5或PI 3 K/Akt信号可能是治疗甲状腺癌的一种新的治疗策略。溶血磷脂酸受体5（LPAR 5）在甲状腺癌中表达上调，并通过直接激活PI 3 K激酶在甲状腺癌的增殖和迁移中发挥重要作用。抑制LPAR 5或PI 3 K/Akt通路可用于治疗表达高水平LPAR 5的转移性和复发性甲状腺癌。
Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC), especially in BRAF‐like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5‐specific antagonist TC LPA5 4 treatment inhibited CGTH‐W3, TPC‐1, B‐CPAP, and BHT‐101 cell proliferation, CGTH‐W3 and TPC‐1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH‐W3 xenograft growth in nude mice. We also found that LPAR5‐specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH‐W3 and TPC‐1 cells. Stimulating CGTH‐W3 cells transfected with pEGFPC1‐Grp1‐PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)‐triphosphate, which indicates that PI3K was activated by LPA directly. The p110β‐siRNA instead of p110α‐siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer. Lysophosphatidic acid receptor 5 (LPAR5) is upregulated in thyroid cancer and plays important roles in thyroid cancer proliferation and migration through activating PI3K kinase directly. Inhibition of LPAR5 or the PI3K/Akt pathway may be used for the therapy of metastatic and recurrent thyroid cancer expressing high levels of LPAR5.
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影响因子：
4.8
作者：
Chen, Guang;Chen, Si-Meng;Meng, Ling-Hua
通讯作者：
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影响因子：
5.8
作者：
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Goldenberg, David
DOI：
10.6004/jnccn.2018.0089
发表时间：
2018-12-01
影响因子：
13.4
作者：
Haddad, Robert I.;Nasr, Christian;Gurski, Lisa A.
通讯作者：
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影响因子：
13.5
作者：
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影响因子：
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作者：
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通讯作者：
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