BackgroundEnhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets.ResultsUsing functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival.ConclusionsOur data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.

中文翻译：

---

抑制脂肪酸去饱和对代谢受损环境中的癌细胞存活有害

背景增强的大分子生物合成是癌细胞生长和增殖不可或缺的一部分。已预测脂质生物合成是癌细胞中的重要过程。然而，尚不清楚该途径中的哪些酶为癌细胞提供最佳选择性并可能成为合适的治疗靶点。结果使用功能基因组学，我们确定了硬脂酰辅酶 A 去饱和酶 (SCD)，一种控制不饱和脂肪酸合成的酶，是必不可少的在乳腺癌和前列腺癌细胞中。在没有外源性脂质的情况下，SCD 抑制改变了细胞脂质组成并阻碍了细胞活力。SCD 抑制也改变了心磷脂的组成，导致细胞色素 C 的释放和细胞凋亡的诱导。此外，SCD 是在球状培养物中生长的癌细胞中产生多不饱和脂质所必需的，这些脂质类似于在肿瘤组织中发现的那些。我们还发现 SCD mRNA 和蛋白质表达在人类乳腺癌中升高，并预示着在高级别肿瘤中的存活率很低。最后，前列腺正移植物中 SCD 的沉默有效地阻止了肿瘤生长并显着增加了动物存活率。结论我们的数据表明脂质去饱和是癌细胞存活的一个重要过程，并表明靶向 SCD 可以有效地限制肿瘤扩张，特别是在代谢受损的条件下肿瘤微环境。我们还发现 SCD mRNA 和蛋白质表达在人类乳腺癌中升高，并预示着在高级别肿瘤中的存活率很低。最后，前列腺正移植物中 SCD 的沉默有效地阻止了肿瘤生长并显着增加了动物存活率。结论我们的数据表明脂质去饱和是癌细胞存活的一个重要过程，并表明靶向 SCD 可以有效地限制肿瘤扩张，特别是在代谢受损的条件下肿瘤微环境。我们还发现 SCD mRNA 和蛋白质表达在人类乳腺癌中升高，并预示着在高级别肿瘤中的存活率很低。最后，前列腺正移植物中 SCD 的沉默有效地阻止了肿瘤生长并显着增加了动物存活率。结论我们的数据表明脂质去饱和是癌细胞存活的一个重要过程，并表明靶向 SCD 可以有效地限制肿瘤扩张，特别是在代谢受损的条件下肿瘤微环境。