Lipid metabolic abnormalities have received intensified concerns and increased de novo synthesis of lipids is recognized as a common feature of many human cancers. Nevertheless, the role of lipid metabolism that confers aggressive properties on human cancers still remains to be revealed. Natural compounds represent an abundant pool of agents for the discovery of novel lead compounds. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes. Here, we assess the association of stearoyl-CoA desaturase 1 (SCD-1) over-expression with malignant progression of colorectal cancer (CRC). Based on this association, the effect of TCN on migration and invasion of colon carcinoma cells closely related to the inhibition of SCD-1 is evaluated. We further demonstrate that reduced production of unsaturated fatty acids (FAs) by blocking SCD-1 activity is beneficial for the anti-invasion effect of TCN. The aim of this study was to clarify the mechanistic connection between metabolite alterations induced by metabolic rewiring and the aggressive tumor phenotype and further develop novel pharmacological tools for the intervention of tumor invasion associated with SCD-1-mediated metabolite alterations.

中文翻译：

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天花霉素抑制与SCD-1介导的代谢物改变相关的结肠癌的侵袭和转移。

脂质代谢异常已引起越来越多的关注，脂质的从头合成增加被认为是许多人类癌症的共同特征。然而，脂质代谢赋予人类癌症侵略性的作用仍有待揭示。天然化合物代表了用于发现新型先导化合物的大量试剂。天花粉蛋白（TCN）是一种倍半萜类化合物，起源于草药植物Maytenus hookeri Loes的内生真菌。在这里，我们评估硬脂酰辅酶A去饱和酶1（SCD-1）的过表达与结直肠癌（CRC）恶性进展的关系。基于这种联系，评估了TCN对结肠癌细胞迁移和侵袭的影响，该细胞与SCD-1的抑制密切相关。我们进一步证明，通过阻断SCD-1活性来减少不饱和脂肪酸（FAs）的产生对TCN的抗侵袭作用是有益的。这项研究的目的是阐明代谢重新布线引起的代谢物改变与侵袭性肿瘤表型之间的机制联系，并进一步开发新的药理学工具来干预与SCD-1介导的代谢物改变有关的肿瘤侵袭。