Department of Urology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518000, Guangdong, China.
Shantou University Medical College, Shantou 515041, China.
Int J Biol Sci. 2019 Jun 4;15(8):1610-1617. doi: 10.7150/ijbs.32518. eCollection 2019.
Fatty acid synthesis is regulated by transcription factors SREBPs and their escort protein SCAP. Malignant cells become dependent on de novo lipogenesis, which sustains rapid proliferation and resistance to cellular stress. Increasing evidence showed SCAP participated in various disease processes including malignant tumors, which regulate transcription factors SREBPs Tumorigenesis is associated with incur glucose consumption and lipogenesis. In our study, we discovered that SCAP was upregulated in BC tissues. SCAP knockdown by CRISPR-Cas9 inhibit the cell proliferation, invasion and migration. Additionally, the cell apoptosis was facilitated. What's more, downregulation of SCAP could weaken the cancer-promoting effects of estrogen on BC. Our study revealed that SCAP played a carcinogenic role in BC and lipogenesis might promote the initiation of BC by inducing SCAP. Thus, Targeting SCAP may provide a promising means of treating BC and a new perspective for the tumorigenesis of bladder cancer.
脂肪酸合成受转录因子 SREBPs 和其伴侣蛋白 SCAP 调节。恶性细胞依赖从头合成脂质,以维持快速增殖和抵抗细胞应激。越来越多的证据表明,SCAP 参与了包括恶性肿瘤在内的各种疾病过程,调节转录因子 SREBPs 的活性。肿瘤发生与葡萄糖消耗和脂肪生成增加有关。在我们的研究中,我们发现 SCAP 在 BC 组织中上调。通过 CRISPR-Cas9 敲低 SCAP 抑制细胞增殖、侵袭和迁移。此外,还促进了细胞凋亡。更重要的是,下调 SCAP 可以减弱雌激素对 BC 的促癌作用。我们的研究表明,SCAP 在 BC 中发挥致癌作用,脂肪生成可能通过诱导 SCAP 促进 BC 的发生。因此,靶向 SCAP 可能为治疗 BC 提供一种有前途的方法,并为膀胱癌的发生提供了一个新的视角。