Trichothecin inhibits invasion and metastasis of colon carcinoma associating with SCD-1-mediated metabolite alteration
Trichothecin inhibits invasion and metastasis of colon carcinoma associating with SCD-1-mediated metabolite alteration
复制标题
单端孢菌素抑制与 SCD-1 介导的代谢物改变相关的结肠癌的侵袭和转移
DOI：
10.1016/j.bbalip.2019.158540
复制
发表时间：
2020-02-01
影响因子：
4.8
通讯作者：
Luo, Xiangjian
中科院分区：
文献类型：
--
作者：
Liao, Chaoliang;Li, Min;Luo, Xiangjian
脂质代谢异常已受到越来越多的关注，并且脂质从头合成的增加被认为是许多人类癌症的共同特征。然而，脂质代谢对人类癌症具有侵袭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丰富药物库。单端孢菌素 (TCN) 是一种倍半萜类化合物，源自草本植物 Maytenus hookeri Loes 的内生真菌。在这里，我们评估了硬脂酰辅酶A去饱和酶 1 (SCD-1) 过度表达与结直肠癌 (CRC) 恶性进展的关系。基于这种关联，评估了TCN对与抑制SCD-1密切相关的结肠癌细胞迁移和侵袭的影响。我们进一步证明，通过阻断SCD-1活性来减少不饱和脂肪酸（FA）的产生有利于TCN的抗侵袭作用。本研究的目的是阐明代谢重连诱导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 介导的代谢物改变相关的肿瘤侵袭。
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 antiinvasion 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.