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.

中文翻译：

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肺癌细胞迁移和转移所需的CERS6。

鞘脂构成了一类生物反应性分子，可以传递信号并在各种细胞类型中表现出多种物理特性，尽管它们在癌症发病机理中的功能尚待阐明。对临床标本和一组细胞系基因表达谱的分析表明，神经酰胺合酶基因CERS6在非小细胞肺癌（NSCLC）组织中过表达，而表达升高则与不良预后和淋巴结相关转移。NSCLC概况和体外荧光素酶分析结果表明，降低的miR-101至少部分促进了CERS6的过表达表达。在降低的CERS6表达条件下，神经酰胺谱发生改变，这被确定与体外细胞迁移和侵袭活性降低有关。此外，CERS6敲低抑制了RAC1阳性的片状脂蛋白/皱纹形成，并减弱了小鼠的肺转移效率，而CERS6的强制表达导致受检细胞系的表型相反。基于这些发现，我们认为CERS6合成的神经酰胺在肺癌的迁移和转移中具有重要作用。