Cafs-Derived Ffa Promotes Oral Cancer By Lipid Raft Synthesis

Cancer-associated fibroblasts (CAFs) are critical for oral squamous cell carcinoma (OSCC) progression. Given that CAFs display elevated lipid metabolic activity and secrete free fatty acids (FFA) to support tumor cells. However, the role of CAFs-derived FFA in anabolic processes and its relationship with lipid raft formation in OSCC cells remain largely unknown. Immunohistochemistry, immunoblotting, FFA quantification, and immunofluorescence were employed to analyze the uptake of CAF-derived FFA and the formation of lipid raft in OSCC cells. Further, cell proliferation, migration, and invasion were assessed by CCK-8, wound healing, and transwell assays. And a lipid raft disruptor, MβCD, was conducted to address the effects of lipid rafts in the tumor biological behaviors. During the OSCC progression, our data showed that the expressions of key lipid synthesis enzymes were up-regulated significantly. In vitro study, we found that the increased lipid synthesis enzymes in CAFs led to the secretion of large amounts of FFA into the extracellular environment. Then, OSCC cells assimilated CAFs-derived FFA to synthesize membrane lipid rafts via activating the potential signaling pathway, leading to promote cell proliferation, migration, and invasion. Of note, the lipid raft disruption inhibited these processes by impairing lipid raft-dependent signaling transduction. OSCC cells would take up CAFs-secreted FFA to promote lipid raft synthesis to support the biological behaviors. It highly depends on the integrity of lipid rafts, suggesting that targeting lipid raft synthesis might be a potential therapeutic strategy for anti-tumor in OSCC.