Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway.
Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway.
复制标题
脂肪酸合酶通过Wnt信号通路调控结直肠癌侵袭和转移
作者：
Wang H;Xi Q;Wu G
脂肪酸合成酶（Fatty acid synthase，Fasn）是脂肪酸合成的关键代谢酶，在多种肿瘤中处于过度活化状态。在这项研究中，我们描述了Fasn在人结直肠癌（CRC）中的表达升高，从而导致淋巴结转移和远处转移以及更晚期的临床表型。遗传干扰表明，敲除Fasn可抑制SW 480和HT 29 CRC细胞系的细胞迁移和侵袭。进一步的机制研究表明，Fasn敲低可通过下调特异性基因Wnt5a、Wnt5b、Fzd2来减弱Wnt信号通路，这至少部分地有助于转移的减少。临床证据证实，在43例CRC患者的队列中，Fasn表达与Wnt信号标志物基因表达呈正相关。总之，我们揭示了在CRC癌变过程中发生的代谢开关，其中Fasn是一个关键因素和潜在的治疗靶点。
Fatty acid synthase (Fasn) is the key metabolic enzyme that accounts for the terminal catalytic step in fatty acid synthesis, which is hyperactivated in various tumors. In this study, we depicted that Fasn expression was elevated in human colorectal cancer (CRC), which accordingly led to lymphatic and distant metastasis and a more advanced clinical phenotype. Genetic perturbations demonstrated that knocking down Fasn inhibited cell migration and invasion both in SW480 and HT29 CRC cell lines. Further mechanical exploration revealed that Fasn knockdown could attenuate Wnt signaling pathway via downregulating distinctive genes, namely Wnt5a, Wnt5b, Fzd2, which at least partly contributed to the decrease in metastasis. Clinical evidence verified a positive correlation between Fasn expression and Wnt signal marker gene expression in a cohort of 43 CRC patients. In conclusion, we shed light on metabolic switches took place during CRC carcinogenesis, among which Fasn is a critical factor and a potential therapeutic target.