Abstract：
Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1 (N-acetyltransferase 1) plays a crucial role in the invasive and metastatic processes of colorectal cancer. The role and molecular mechanism of NAT1 on tumor cells were verified by establishing a cell model of overexpression and knockdown of NAT1, and further verified by establishing a liver metastasis model of colorectal cancer for animal experiments. In vivo and in vitro experiments have demonstrated that overexpression of NAT1 reduces the ability of metastasis and invasion of colorectal cancer cells. NAT1 overexpression inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing the EMT (epithelial-mesenchymal transition) process and glycolytic ability of tumor cells. Additionally, decreased glycolytic ability results in reduced VEGF (Vascular endothelial growth factor) expression in colorectal cancer cells. The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.
摘要：
转移是癌症相关死亡的主要原因，结直肠癌（CRC）肝转移是CRC的主要不良预后因素。NAT1（N-乙酰转移酶1）在大肠癌的侵袭和转移过程中起着至关重要的作用。通过建立NAT1过表达和敲低的细胞模型,验证NAT1对肿瘤细胞的作用和分子机制,并通过建立结直肠癌肝转移模型进行动物实验进一步验证。体内和体外实验表明，NAT1的过表达降低了结直肠癌细胞的转移和侵袭能力。NAT1过表达抑制PI3K/AKT/mTOR信号通路,从而抑制肿瘤细胞的EMT（上皮-间质转化）过程和糖酵解能力。此外,糖酵解能力降低导致结直肠癌细胞VEGF(血管内皮生长因子)表达降低。VEGF表达降低导致肝转移瘤血管生成和血管通透性降低,最终减少肝转移的发生。我们的发现强调NAT1的过表达显著抑制PI3K/AKT/mTOR信号通路,从而抑制EMT，糖酵解能力,和VEGF在大肠癌细胞中的表达，共同预防肝转移的发展。
