Melanoma exhibits high metastatic potential and therapy resistance, driven by metabolic flexibility and structural remodeling. In this study, we performed an integrated analysis of the SK-MEL-30 melanoma cell line using function-focused quantitative proteomics and amino acid profiling. Proteins were quantified using a label-free normalized spectral abundance factor (NSAF) approach, while intracellular amino acids were measured by LC-MS/MS. Functional enrichment analyses based on KEGG and Gene Ontology were used to associate protein expression patterns with metabolic pathways. A total of 148 proteins were identified, predominantly representing high-abundance and functionally relevant components of metabolic and structural pathways. Key cytoskeletal proteins, including vimentin and S100A11, were among the most abundant, consistent with a mesenchymal-like and potentially invasive phenotype. Metabolic profiling revealed elevated expression of glycolytic enzymes such as PKM and LDHA, consistent with a glycolytic shift. Increased levels of l-glutamine and l-glutamic acid, together with GOT2 expression, suggest an active glutamine aspartate axis supporting tricarboxylic acid cycle activity and nitrogen metabolism. In addition, elevated levels of stress-response proteins, including HSP90 and SOD2, indicate a proteostatic network adapted to metabolic stress. Although the proteome coverage is lower than that reported in large-scale deep proteomic studies, the NSAF-based workflow was designed to capture the most abundant and functionally relevant proteins, providing a focused overview of the major metabolic and structural characteristics of SK-MEL-30 melanoma cells. Overall, this integrative analysis highlights the coordination between metabolic reprogramming and cytoskeletal organization in SK-MEL-30 cells and suggests that glutamine-dependent metabolic pathways warrant further investigation as potential therapeutic targets in melanoma.
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