Chao He,Xiuyuan Chen,Ying Chen,Jianying Sun,Manting Qi,Sonia Rocha,Mu Wang
Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.
Yuanyuan Yang,Jiapan Hu,Fan Mei,Yangyang Gan,Qiang Ma,Chuanda Zhu,Lidong Gong,Zhiqiang Lin
Neurodevelopment is a highly coordinated process involving cell differentiation, neurite extension, axon guidance, and dendritic formation, forming the structural basis for cognitive function. Metal ions such as silver and zinc play essential roles in neuronal disease; however, their precise function in neurodevelopment remains elusive. Due to the solubility characteristics of metal ions and the presence of ion channels on the cell membrane, studying the effects of metal ions within cells presents certain challenges. Recent advances in nanotechnology have enabled the effective delivery of goods into cells in a receptor-independent manner. In this study, we developed 11 types of metal ion nanodepots, NanoMIs, a novel class of nanoparticle-based metal ion delivery systems capable of effective intracellular metal ion release and lysosomal escape. These NanoMIs were applied to primary neuronal cells to investigate their effects on neuronal morphology. Our results show that NanoMIs primarily enhance axon elongation by modulating the PFN1-actin-cytoskeleton pathway. These findings suggest that NanoMIs offer a promising approach for exploring the role of metal ions in neuronal development and provide insights into the molecular mechanisms underlying metal-ion-mediated effects in neuronal cells.
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