Zhang Xuedan, Li Xiaoyu, Xiong Guohang, Yun Fang, Feng Yu, Ni Qinxuan, Wu Na, Yang Lijuan, Yi Zihan, Zhang Qiao, Yang Zhe, Kuang Yingmin, Sai Buqing, Zhu Yuechun
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China.
Department of Medical Oncology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming 650500, China.
Metabolites. 2022 Nov 17;12(11):1132. doi: 10.3390/metabo12111132.
A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.
高脂饮食在加重癌症方面起着重要作用。棕榈酸（PA）是饱和脂肪酸的成分之一；据报道，它可促进黑色素瘤中的肿瘤增殖，但棕榈酸介导的信号转导途径仍不清楚。本研究表明，棕榈酸可促进黑色素瘤的肺转移。此外，通过分子对接预测了棕榈酸与Toll样受体4（TLR4）之间的相互作用。实验结果证明，棕榈酸可促进TLR4和含Toll/IL-1受体结构域的接头诱导IFN-β（TRIF）的表达。抑制TLR4后，Pellino1（Peli1）的表达和NF-κB的磷酸化（pNF-κB）下调，沉默Peli1也抑制了NF-κB的磷酸化。因此，我们得出结论，棕榈酸通过TLR4/TRIF-Peli1-pNF-κB途径促进黑色素瘤的肺转移。
