Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.
Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.
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细胞因子信号传导 2 的抑制剂限制 IGF1R 介导的肺腺癌上皮间质转化的调节
DOI：
10.1038/s41419-018-0457-5
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发表时间：
2018-04-01
影响因子：
9
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Zhou Y;Zhang Z;Wang N;Chen J;Zhang X;Guo M;John Zhong L;Wang Q
非小细胞肺癌（NSCLC），包括腺癌和鳞状细胞癌，是肺部恶性肿瘤死亡的主要原因，并且由于转移而具有不良预后。细胞因子信号传导抑制因子-2（SOCS 2）是细胞因子信号传导的反馈抑制剂，已被证明参与生长控制。在这里，我们发现SOCS 2在NSCLC患者的肿瘤病灶中显著下调。SOCS 2的表达水平与临床分期、淋巴结转移、组织学分型及生存期相关。特别是SOCS 2的表达降低与肺腺癌患者的病理分期、淋巴结转移和总生存期明显相关。体内动物实验结果表明，过表达的SOCS 2减弱了肺腺癌的转移特征，包括通过抑制上皮-间质转化（EMT）。进一步的功能研究表明，胰岛素样生长因子1（IGF 1）驱动的肺腺癌细胞的迁移和侵袭行为可以部分抑制外源性SOCS 2表达。对作用机制的研究表明，SOCS 2通过与IGF 1 R上的STAT结合位点竞争性结合，使信号转导和转录激活因子3（STAT 3）和STAT 5失活，从而抑制EMT。总之，我们的研究结果揭示了SOCS 2失调在肺腺癌的致病性中的重要作用，提示其作为诊断肺腺癌的生物标志物的潜在用途，并为开发新的治疗靶点铺平了道路SOCS 2-IGF 1 R-STAT在肺腺癌中的轴。
Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma, is the leading cause of death from lung malignancies and has a poor prognosis due to metastasis. Suppressor of cytokine signalling-2 (SOCS2), a feedback inhibitor of cytokine signalling, has been shown to be involved in growth control. Here, we show that SOCS2 were significantly downregulated in tumour foci in NSCLC patients. The expression levels of SOCS2 significantly correlated with clinical stage, lymph node metastasis, histological subtype and survival time. In particular, the decreased expression of SOCS2 significantly associated with advanced pathological stage, lymph node metastasis and shorter overall survival in lung adenocarcinoma patients. In vivo animal results showed that overexpressed SOCS2 attenuated the metastatic characteristics of lung adenocarcinoma, including by inhibiting the epithelial–mesenchymal transition (EMT). Further functional studies indicated that insulin-like growth factor 1 (IGF1)-driven migratory and invasive behaviours of lung adenocarcinoma cells can be partially suppressed by exogenous SOCS2 expression. Investigations into the mechanism of action revealed that SOCS2 inhibits EMT by inactivating signal transducer and activator of transcription 3 (STAT3) and STAT5 via the competitive binding of SOCS2 to the STAT binding sites on IGF1R. Altogether, our results reveal an important role for SOCS2 dysregulation in the pathogenicity of lung adenocarcinoma, suggest its potential use as a biomarker for diagnosing lung adenocarcinoma, and paves the way to develop novel therapy targets as the axis of SOCS2–IGF1R–STAT in lung adenocarcinoma.
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影响因子：
19.6
作者：
Isshiki, Keiji;He, Zhiheng;Maeno, Yasuhiro;Ma, Ronald C.;Yasuda, Yutaka;Kuroki, Tatsuya;White, Gregory S.;Patti, Mary E.;Weir, Gordon C.;King, George L.
通讯作者：
King, George L.
影响因子：
37.3
作者：
Min HY;Yun HJ;Lee JS;Lee HJ;Cho J;Jang HJ;Park SH;Liu D;Oh SH;Lee JJ;Wistuba II;Lee HY
通讯作者：
Lee HY
DOI：
10.1158/1078-0432.ccr-11-1889
发表时间：
2012-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sen B;Peng S;Woods DM;Wistuba I;Bell D;El-Naggar AK;Lai SY;Johnson FM
通讯作者：
Johnson FM
DOI：
10.1158/1078-0432.ccr-12-0912
发表时间：
2012-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arcila ME;Chaft JE;Nafa K;Roy-Chowdhuri S;Lau C;Zaidinski M;Paik PK;Zakowski MF;Kris MG;Ladanyi M
通讯作者：
Ladanyi M
影响因子：
5.7
作者：
Lee, TL;Yeh, J;Chen, Z
通讯作者：
Chen, Z