Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway

  • Metabolites. 2022 Nov 17;12(11):1132. doi: 10.3390/metabo12111132.
Xuedan Zhang  1 Xiaoyu Li  1 Guohang Xiong  1 Fang Yun  1 Yu Feng  1 Qinxuan Ni  1 Na Wu  1 Lijuan Yang  1 Zihan Yi  2 Qiao Zhang  1 Zhe Yang  3 Yingmin Kuang  4 Buqing Sai  1 Yuechun Zhu  1
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China.
  • 2. Department of Medical Oncology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming 650500, China.
  • 3. Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
  • 4. Department of Organ Transplantation, The First Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
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.

Keywords
TLR4/TRIF-Peli1-pNF-κB axis; melanoma; palmitic acid.
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