Abstract：
Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.
摘要：
胆管癌是一种治疗选择有限的致命疾病。我们筛选了胆管癌致瘤性所需的基因，并鉴定了一种δ-6去饱和酶FADS2。FADS2耗竭降低了体内致瘤性和细胞增殖。在临床样本中，FADS2在癌细胞中表达，但在基质细胞中不表达。FADS2抑制还降低了细胞的迁移和球体形成能力，并增加了凋亡性细胞死亡和铁凋亡标志物。脂质测定显示，FADS2敲低细胞中甘油三酯和胆固醇酯水平降低。在FADS2耗尽的细胞中,耗氧比率也降低。这些数据表明，FADS2消耗导致脂质水平降低，导致能量产生减少和癌细胞恶性肿瘤的减弱。
