Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway
Xuedan Zhang, Xiaoyu Li, Guohang Xiong, Fang Yun, Feng Yu, Qinxuan Ni, Na Wu, Lijuan Yang, Zihan Yi, Qiao Zhang, Zhe Yang, Yingmin Kuang, Buqing Sai, Yuechun Zhu
Abstract
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.