EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer.
EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer.
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EGFR 通过磷酸化肺癌中的 SCD1 来调节单不饱和脂肪酸的合成。
DOI：
10.1186/s12943-017-0704-x
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发表时间：
2017-07-19
期刊：
影响因子：
37.3
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Zhang J;Song F;Zhao X;Jiang H;Wu X;Wang B;Zhou M;Tian M;Shi B;Wang H;Jia Y;Wang H;Pan X;Li Z
表皮生长因子受体（EGFR）是一种众所周知的致癌驱动因素，有助于广泛的癌症类型的启动和发展。异常脂质代谢，包括高度生产的单不饱和脂肪酸（MUFA）被认为是癌症的标志。但是，EGFR如何调节癌症中的MUFA合成仍然难以捉摸。这是我们研究的重点。
EGFR和stearoyl-COA去饱和酶-1（SCD1）之间的相互作用被视为免疫沉淀。通过蛋白质印迹测试了SCD1蛋白表达，稳定性和磷酸化。 MUFA的合成是通过液相色谱 - 质谱法确定的。通过CCK-8测定，膜联蛋白V/PI染色，菌落形成测定和皮下注射异种移植分析检测到肺癌的生长。激活的EGFR，磷酸化和总SCD1的表达通过90个非小细胞肺取消样本中的免疫组织化学测试。通过卡方检验，Kaplan-Meier存活曲线分析和COX回归分析临床相关性。
EGFR与Y55的SCD1结合并磷酸化。 Y55的磷酸化是维持SCD1蛋白稳定性所必需的，因此增加了MUFA水平以促进肺癌的生长。此外，EGFR刺激的癌症生长取决于SCD1活性。评估非小细胞肺癌的评估表明，EGFR激活，SCD1 Y55磷酸化和SCD1蛋白表达之间存在正相关。此外，磷酸-SCD1 Y55可以作为患者生存不良的独立预后因素。
我们的研究表明，EGFR通过Y55磷酸化稳定SCD1，从而上调MUFA合成以促进肺癌的生长。因此，我们提供了第一个证据，表明SCD1可以通过酪氨酸磷酸化巧妙地控制，并发现了肺癌中致癌受体酪氨酸激酶和脂质代谢之间以前未知的直接连接。我们还建议SCD1 Y55磷酸化作为肺癌的潜在诊断标记。
本文的在线版本（DOI：10.1186/S12943-017-0704-X）包含补充材料，可供授权用户使用。
Epidermal growth factor receptor (EGFR), a well-known oncogenic driver, contributes to the initiation and progression of a wide range of cancer types. Aberrant lipid metabolism including highly produced monounsaturated fatty acids (MUFA) is recognized as a hallmark of cancer. However, how EGFR regulates MUFA synthesis in cancer remains elusive. This is the focus of our study. The interaction between EGFR and stearoyl-CoA desaturase-1 (SCD1) was detected byco-immunoprecipitation. SCD1 protein expression, stability and phosphorylation were tested by western blot. The synthesis of MUFA was determined by liquid chromatography-mass spectrometry. The growth of lung cancer was detected by CCK-8 assay, Annexin V/PI staining, colony formation assay and subcutaneous xenograft assay. The expression of activated EGFR, phosphorylated and total SCD1 was tested by immunohistochemistry in 90 non-small cell lung cancersamples. The clinical correlations were analyzed by Chi-square test, Kaplan-Meier survival curve analysis and Cox regression. EGFR binds to and phosphorylates SCD1 at Y55. Phosphorylation of Y55 is required for maintaining SCD1 protein stability and thus increases MUFA level to facilitate lung cancer growth. Moreover, EGFR-stimulated cancer growth depends on SCD1 activity. Evaluation of non-small cell lung cancersamples reveals a positive correlation among EGFR activation, SCD1 Y55 phosphorylation and SCD1 protein expression. Furthermore, phospho-SCD1 Y55 can serve as an independent prognostic factor for poor patient survival. Ourstudy demonstrates that EGFR stabilizes SCD1 through Y55 phosphorylation, thereby up-regulating MUFA synthesis to promote lung cancer growth. Thus, we provide the first evidence that SCD1 can be subtly controlled by tyrosine phosphorylation and uncover a previously unknown direct linkage between oncogenic receptor tyrosine kinase and lipid metabolism in lung cancer. We also propose SCD1 Y55 phosphorylation as a potential diagnostic marker for lung cancer. The online version of this article (doi:10.1186/s12943-017-0704-x) contains supplementary material, which is available to authorized users.
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影响因子：
11.8
作者：
Chou, Ruey-Hwang;Wang, Ying-Nai;Hsieh, Yi-Hsien;Li, Long-Yuan;Xia, Weiya;Chang, Wei-Chao;Chang, Ling-Chu;Cheng, Chien-Chia;Lai, Chien-Chen;Hsu, Jennifer L.;Chang, Wei-Jung;Chiang, Shu-Ya;Lee, Hong-Jen;Liao, Hsin-Wei;Chuang, Pei-Huan;Chen, Hui-Yu;Wang, Hung-Ling;Kuo, Sheng-Chu;Chen, Chung-Hsuan;Yu, Yung-Luen;Hung, Mien-Chie
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影响因子：
5.2
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影响因子：
158.5
作者：
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通讯作者：
Haber, DA
影响因子：
3.7
作者：
Ide Y;Waki M;Hayasaka T;Nishio T;Morita Y;Tanaka H;Sasaki T;Koizumi K;Matsunuma R;Hosokawa Y;Ogura H;Shiiya N;Setou M
通讯作者：
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影响因子：
28.2
作者：
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通讯作者：
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