School of Basic Medical Sciences, Hebei University of Chinese Medicine. Shijiazhuang, Hebei, China.
School of Basic Medical Sciences, Hebei University of Chinese Medicine. Shijiazhuang, Hebei, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, China.
Biochem Biophys Res Commun. 2024 Dec 3;736:150494. doi: 10.1016/j.bbrc.2024.150494. Epub 2024 Aug 5.
Colorectal cancer (CRC) is recognized as the third most common form of malignancy, with the liver frequently serving as the main site for metastasis. Anoikis resistance (AR) is critical in colorectal cancer liver metastases (CRLM). Fatty acid synthase (FASN), essential in lipid synthesis, mediates AR in many cancers. The present research examines the function of FASN in ERK1/2-mediated AR in CRLM and evaluates its therapeutic potential.
We performed scratch and migration experiment to evaluate the migration capacity of the LoVo cells. Flow cytometry was employed to identify cell apoptosis. The levels of FASN, p-ERK1/2, and proteins related to apoptosis was analyzed by Western blot. The mRNA level of FASN was determined by q-PCR after FASN silencing. In addition, we used an intrasplenic liver metastasis model of nude to assess the effect of FASN on CRLM.
In vitro experiments showed that after FASN silencing, the cell apoptosis rate was increased, migration capability was notably decreased, the expression of p-ERK1/2, the proteins related to anti-apoptotic were significantly decreased, and the proteins related to apoptosis were significantly increased. In vivo experiments showed that AR significantly increased the number of liver metastatic foci, whereas FASN silencing significantly inhibited CRLM.
These results suggest that FASN silencing suppressed AR through the ERK 1/2 pathway, which in turn suppressed CRLM.
结直肠癌（CRC）是最常见的恶性肿瘤之一，肝脏通常是转移的主要部位。抗凋亡（AR）在结直肠癌肝转移（CRLM）中起着至关重要的作用。脂肪酸合酶（FASN）在脂质合成中必不可少，它在许多癌症中介导 AR。本研究探讨了 FASN 在 ERK1/2 介导的 CRLM 中的作用及其治疗潜力。
我们通过划痕和迁移实验评估 LoVo 细胞的迁移能力。通过流式细胞术鉴定细胞凋亡。通过 Western blot 分析 FASN、p-ERK1/2 和与凋亡相关的蛋白质水平。沉默 FASN 后通过 q-PCR 测定 FASN 的 mRNA 水平。此外，我们使用裸鼠脾内肝转移模型评估 FASN 对 CRLM 的影响。
体外实验表明，沉默 FASN 后，细胞凋亡率增加，迁移能力明显下降，p-ERK1/2 表达、抗凋亡相关蛋白明显减少，凋亡相关蛋白明显增加。体内实验表明，AR 显著增加肝转移灶数量，而 FASN 沉默则显著抑制 CRLM。
这些结果表明，沉默 FASN 通过 ERK1/2 通路抑制 AR，从而抑制 CRLM。
