| Popis: |
High-fat environment facilitates the metastasis of lung adenocarcinoma (LUAD) with unknown mechanism. This work aims to reveal the role of fatty acid transporter CD36 in LUAD cell metastasis upon fatty acid oversupply. In human LUAD cells, palmitic acid (PA) treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Nude mice fed with normal-chew diet (NCD) and high-fat diet (HFD) were subcutaneously injected with scramble/CD36-shRNA stable tranfected-A549 cells respectively. Compared with NCD mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential in a CD36-dependent manner, which accompanied by obvious sarcolemmal actin remodeling. Consistently, xenografted and tail vein-injected scramble RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. Collectively, our finding demonstrates that CD36 initiates the Src signal transduction to induce actin remodeling in high fat environment, which in turn promotes LUAD cell metastasis. Our finding provides valuable targets for prevention and treatment of LUAD. |
