代谢重编程是转化细胞的普遍特征，是癌症的标志之一，并使肿瘤细胞能够适应新环境。积累的证据表明，一些肿瘤细胞无法将 6-磷酸甘露糖转化为 6-磷酸果糖，从而损害了 6-磷酸甘露糖异构酶 (MPI) 水平低的细胞中的肿瘤生长。因此，我们进行了功能分析，并描绘了接受甘露糖处理的具有不同突变背景的黑色素瘤细胞系的蛋白质组景观和蛋白酶底物（降解组）的库。我们的结果表明，甘露糖处理后黑色素瘤细胞系的蛋白质组和降解组发生显着重排，包括分解代谢途径的激活（例如蛋白质周转）和蛋白质 N 末端乙酰化的差异。尽管 MPI 蛋白丰度和基因表达状态不是预后标志物，但外源单糖来源（即甘露糖）引起的网络扰动显着影响下游互连的生物回路。因此，正如本研究所报道的，由于 MPI 酶的功能状态引起的代谢重连而对甘露糖下游效应进行蛋白质组/降解组图谱分析，可能有助于识别黑色素瘤中受影响的信号通路中的特定分子参与者。

Metabolic reprogramming is a ubiquitous feature of transformed cells, comprising one of the hallmarks of cancer and enabling neoplastic cells to adapt to new environments. Accumulated evidence reports on the failure of some neoplastic cells to convert mannose-6-phosphate into fructose-6-phosphate, thereby impairing tumor growth in cells displaying low levels of mannose-6-phosphate isomerase (MPI). Thus, we performed functional analyses and profiled the proteome landscape and the repertoire of substrates of proteases (degradome) of melanoma cell lines with distinct mutational backgrounds submitted to treatment with mannose. Our results suggest a significant rearrangement in the proteome and degradome of melanoma cell lines upon mannose treatment including the activation of catabolic pathways (such as protein turnover) and differences in protein N-terminal acetylation. Even though MPI protein abundance and gene expression status are not prognostic markers, perturbation in the network caused by an exogenous monosaccharide source (i.e., mannose) significantly affected the downstream interconnected biological circuitry. Therefore, as reported in this study, the proteomic/degradomic mapping of mannose downstream effects due to the metabolic rewiring caused by the functional status of the MPI enzyme could lead to the identification of specific molecular players from affected signaling circuits in melanoma.