Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN.
Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN.
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硬脂酰辅酶A去饱和酶-1通过抑制PTEN促进结直肠癌响应葡萄糖的转移
DOI：
10.1186/s13046-018-0711-9
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发表时间：
2018-03-12
期刊：
影响因子：
--
通讯作者：
Su Q
中科院分区：
文献类型：
--
作者：
Ran H;Zhu Y;Deng R;Zhang Q;Liu X;Feng M;Zhong J;Lin S;Tong X;Su Q
研究背景糖尿病患者是结直肠癌（CRC）转移的高危因素，硬脂酰辅酶A去饱和酶1（stearoyl-CoA desaturase 1，SCD 1）是由饱和脂肪酸转化为单不饱和脂肪酸（monounsaturated fatty acids，MUFA）的主要酶，在糖尿病和结直肠癌患者中常发生失调。SCD 1在结直肠癌转移中的功能和机制及其与葡萄糖的关系在很大程度上仍不清楚。 https://genome-cancer.ucsc.edu/ ).建立稳定转染SCD 1 shRNA或载体的CRC细胞系，以研究SCD 1在调节CRC细胞迁移和侵袭中的作用。设置一个葡萄糖浓度梯度，以探讨调节SCD 1在结直肠癌相关的糖尿病conditions.ResultsThe临床数据分析显示，高表达的SCD 1在结直肠癌组织与结直肠癌的预后呈负相关。体外实验表明，SCD 1通过促进上皮-间质转化（EMT）促进CRC进展。脂质组学分析表明，SCD 1增加MUFA水平和MUFA管理可以挽救SCD 1敲低诱导的CRC细胞迁移和侵袭缺陷。此外，高糖刺激下，碳水化合物反应元件结合蛋白（ChREBP）可促进SCD 1介导的CRC进展。从机制上看，高糖血症-SCD 1-MUFA通过调节PTEN诱导结直肠癌细胞的迁移和侵袭。结论SCD 1通过产生MUFA和抑制葡萄糖诱导的PTEN，促进结直肠癌细胞的转移，这可能是糖尿病诱导结直肠癌转移的一种新机制。
BackgroundDiabetic patients have a higher risk factor forcolorectal cancer (CRC)metastasis.Stearoyl-CoA desaturase 1 (SCD1), the main enzyme responsible for producingmonounsaturated fatty acids(MUFA)from saturated fatty acids, is frequently deregulated in both diabetes andCRC. The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown.MethodsSCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer.ucsc.edu/ ). CRC cell lines stably transfected with SCD1 shRNAs or vector were established to investigate the role of SCD1 in modulating migration and invasion of CRC cells. A glucose concentration gradient was set to investigate regulation of SCD1 in CRC relevant to diabetic conditions.ResultsThe clinical data analysis showed high expression of SCD1 in CRC tissues with a negative correlation with the prognosis of CRC. In vitro experiments revealed that SCD1 increased CRC progression through promotingepithelial–mesenchymal transition (EMT). Lipidomic analysis demonstrated that SCD1 increased MUFA levels and MUFA administration could rescue migration and invasion defect of CRC cells induced by SCD1 knockdown. Furthermore, SCD1-mediated progression of CRC was promoted bycarbohydrate response-element binding protein (ChREBP)in response to high glucose. Mechanistically, hyperglycemia-SCD1-MUFA induced CRC cell migration and invasion by regulating PTEN.ConclusionsOur findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.
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影响因子：
4
作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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DOI：
10.1016/j.bbagen.2017.02.024
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