The membrane bile acid receptor TGR5 drives cell growth and migration via activation of the JAK2/STAT3 signaling, pathway. in non-small cell lung cancer
The membrane bile acid receptor TGR5 drives cell growth and migration via activation of the JAK2/STAT3 signaling, pathway. in non-small cell lung cancer
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非小细胞肺癌中膜胆汁酸受体 TGR5 通过激活 JAK2/STAT3 信号通路驱动细胞生长和迁移
DOI：
10.1016/j.canlet.2017.10.017
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Jiang, Handong
中科院分区：
文献类型：
--
作者：
Liu, Xueqing;Chen, Bi;Jiang, Handong
越来越多的证据表明，一种新兴的G蛋白偶联受体TGR 5在从代谢疾病到癌症的各种疾病中发挥着至关重要的作用。然而，TGR 5在非小细胞肺癌（NSCLC）中的生物学功能仍然难以捉摸。我们发现TGR 5在NSCLC中异常表达，并且与NSCLC患者的晚期临床分期呈正相关。我们进一步发现，TGR 5敲低阻止JAK 2和STAT 3磷酸化，并抑制STAT 3靶基因的表达，从而抑制NSCLC中的细胞增殖、迁移和侵袭。此外，TGR 5的促进作用被JAK 2抑制剂或STAT 3敲低显著逆转。此外，我们证明了NSCLC组织样本中TGR 5和p-STAT 3表达之间的正相关性。TGR 5和p-STAT 3同时高表达的患者预后最差。此外，NSCLC患者血清中脱氧胆酸（DCA）、熊去氧胆酸（UDCA）和鹅去氧胆酸（CDCA）水平均显著高于健康对照组，且血清DCA水平越高，TGR 5表达越强。此外，DCA通过TGR 5依赖的方式显著促进NSCLC细胞的迁移和侵袭。综上所述，这些结果表明TGR 5通过JAK 2/STAT 3信号通路驱动NSCLC中的细胞生长和迁移。(C)2017爱思唯尔B. V.保留所有权利。
Mounting evidence suggests that an emerging G protein-coupled receptor, TGR5, plays a crucial role ranging from metabolic diseases to cancers. However, the biological functions of TGR5 in non-small cell lung cancer (NSCLC) remain elusive. We found that TGR5 was aberrantly expressed in NSCLC and positively correlated with an advanced clinical stage in NSCLC patients. We further discovered that TGR5 knockdown prevented JAK2 and STAT3 phosphorylation and repressed the expression of STAT3 target genes, thus inhibiting cell proliferation, migration and invasion in NSCLC. Moreover, the promotive effects of TGR5 were significantly reversed by a JAK2 inhibitor or STAT3 knockdown. Additionally, we demonstrated a positive correlation between TGR5 and p-STAT3 expression in NSCLC tissue samples. Patients with both high TGR5 and p-STAT3 expression had the worst prognosis. In addition, the serum levels of deoxycholic acid (DCA), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in NSCLC patients were much higher than those in the healthy controls and the patients with higher serum DCA levels had stronger TGR5 expression simultaneously. Moreover, DCA markedly promoted NSCLC cell migration and invasion through a TGR5-dependent way. Taken together, these results indicate that TGR5 drives cell growth and migration through JAK2/STAT3 signaling pathway in NSCLC. (C) 2017 Elsevier B.V. All rights reserved.