Mannose-6-Phosphate Isomerase Functional Status Shapes a Rearrangement in the Proteome and Degradome of Mannose-Treated Melanoma Cells

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, t...

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Published in:	Journal of proteome research Vol. 23; no. 11; pp. 5177 - 5192
Main Authors:	de Vasconcellos Racorti, Nathália, Martinelli, Matheus, Bustos, Silvina Odete, Salardani, Murilo, Camacho, Maurício Frota, Barcick, Uilla, Fonseca Lima, Luis Roberto, Jedlicka, Letícia Dias Lima, Ladeira de Campos, Claudia Barbosa, Valente, Richard Hemmi, Chammas, Roger, Zelanis, André
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 01-11-2024
Subjects:	Acetylation - drug effects Cell Line, Tumor Humans Mannose - metabolism Mannose-6-Phosphate Isomerase - genetics Mannose-6-Phosphate Isomerase - metabolism Melanoma - genetics Melanoma - metabolism Proteome - metabolism Proteomics - methods metabolic rewiring phosphomannose isomerase melanoma degradomics proteomics
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1535-3893 1535-3907 1535-3907
DOI:	10.1021/acs.jproteome.4c00705