CERS6 required for cell migration and metastasis in lung cancer.
CERS6 required for cell migration and metastasis in lung cancer.
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DOI：
10.1111/jcmm.15817
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
Takahashi T
中科院分区：
文献类型：
--
作者：
Suzuki M;Cao K;Kato S;Mizutani N;Tanaka K;Arima C;Tai MC;Nakatani N;Yanagisawa K;Takeuchi T;Shi H;Mizutani Y;Niimi A;Taniguchi T;Fukui T;Yokoi K;Wakahara K;Hasegawa Y;Mizutani Y;Iwaki S;Fujii S;Satou A;Tamiya-Koizumi K;Murate T;Kyogashima M;Tomida S;Takahashi T
鞘脂是一类生物活性分子，在各种细胞类型中传递信号并表现出各种物理特性，尽管它们在癌症发病机制中的功能尚未阐明。临床标本和一组细胞系的基因表达谱分析显示，神经酰胺合成酶基因CERS6在非小细胞肺癌（NSCLC）组织中过度表达，而表达升高与预后不良和淋巴结转移有关。NSCLC特征和体外荧光素酶分析结果表明，至少在一定程度上，miR - 101表达的降低促进了CERS6的过表达。在CERS6表达降低的条件下，神经酰胺谱发生改变，这与体外细胞迁移和侵袭活性降低有关。此外，在小鼠中，敲低CERS6抑制了RAC1阳性板足/褶叶的形成并减弱了肺转移效率，而在所检查的细胞系中，强迫表达CERS6导致相反的表型。基于这些发现，我们认为CERS6的神经酰胺合成在肺癌的迁移和转移中具有重要作用。
Sphingolipids constitute a class of bio‐reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non–small‐cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR‐101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1‐positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.
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