{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:11:54Z","timestamp":1791562314333,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","award":["18493"],"award-info":[{"award-number":["18493"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale","award":["18493"],"award-info":[{"award-number":["18493"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b2-Galactosylceramidase (GALC) is a lysosomal enzyme involved in sphingolipid metabolism by removing \u03b2-galactosyl moieties from \u03b2-galactosylceramide and \u03b2-galactosylsphingosine. Previous observations have shown that GALC may exert pro-oncogenic functions in melanoma and Galc silencing, leading to decreased oncogenic activity in murine B16 melanoma cells. The tumor-driving BRAF(V600E) mutation is present in approximately 50% of human melanomas and represents a major therapeutic target. However, such mutation is missing in melanoma B16 cells. Thus, to assess the impact of GALC in human melanoma in a more relevant BRAF-mutated background, we investigated the effect of GALC overexpression on the proteomic landscape of A2058 and A375 human melanoma cells harboring the BRAF(V600E) mutation. The results obtained by liquid chromatography-tandem mass spectrometry (LC-MS\/MS) demonstrate that significant differences exist in the protein landscape expressed under identical cell culture conditions by A2058 and A375 human melanoma cells, both harboring the same BRAF(V600E)-activating mutation. GALC overexpression resulted in a stronger impact on the proteomic profile of A375 cells when compared to A2058 cells (261 upregulated and 184 downregulated proteins versus 36 and 14 proteins for the two cell types, respectively). Among them, 25 proteins appeared to be upregulated in both A2058-upGALC and A375-upGALC cells, whereas two proteins were significantly downregulated in both GALC-overexpressing cell types. These proteins appear to be involved in melanoma biology, tumor invasion and metastatic dissemination, tumor immune escape, mitochondrial antioxidant activity, endoplasmic reticulum stress responses, autophagy, and\/or apoptosis. Notably, analysis of the expression of the corresponding genes in human skin cutaneous melanoma samples (TCGA, Firehose Legacy) using the cBioPortal for Cancer Genomics platform demonstrated a positive correlation between GALC expression and the expression levels of 14 out of the 27 genes investigated, thus supporting the proteomic findings. Overall, these data indicate for the first time that the expression of the lysosomal sphingolipid-metabolizing enzyme GALC may exert a pro-oncogenic impact on the proteomic landscape in BRAF-mutated human melanoma.<\/jats:p>","DOI":"10.3390\/ijms241310555","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"10555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Pro-Oncogenic Sphingolipid-Metabolizing Enzyme \u03b2-Galactosylceramidase Modulates the Proteomic Landscape in BRAF(V600E)-Mutated Human Melanoma Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-8136","authenticated-orcid":false,"given":"Davide","family":"Capoferri","sequence":"first","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Chiodelli","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Corli","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Belleri","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Scalvini","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mignani","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Guerra","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-0607","authenticated-orcid":false,"given":"Elisabetta","family":"Grillo","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"De Giorgis","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Center for Allergic and Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Center for Allergic and Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-8376","authenticated-orcid":false,"given":"Marco","family":"Presta","sequence":"additional","affiliation":[{"name":"Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Consorzio Interuniversitario Biotecnologie (CIB), Unit of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1158\/0008-5472.CAN-19-3382","article-title":"\u03b2-galactosylceramidase promotes melanoma growth via modulation of ceramide metabolism","volume":"80","author":"Belleri","year":"2020","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747333","DOI":"10.3389\/fmed.2021.747333","article-title":"Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery","volume":"8","author":"Kwon","year":"2021","journal-title":"Front. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41416-018-0227-2","article-title":"Proteomic phenotyping of metastatic melanoma reveals putative signatures of MEK inhibitor response and prognosis","volume":"119","author":"Krisp","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cell.2019.08.012","article-title":"Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence","volume":"179","author":"Harel","year":"2019","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1061832","DOI":"10.3389\/fonc.2022.1061832","article-title":"New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma","volume":"12","author":"Militaru","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1479-5876-10-85","article-title":"The role of BRAF V600 mutation in melanoma","volume":"10","author":"Ascierto","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/sj.onc.1207405","article-title":"Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines","volume":"23","author":"Melnikova","year":"2004","journal-title":"Oncogene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e451","DOI":"10.1002\/ctm2.451","article-title":"The Human Melanoma Proteome Atlas\u2014Complementing the melanoma transcriptome","volume":"11","author":"Betancourt","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Jung","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/s41589-019-0399-y","article-title":"ABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5","volume":"15","author":"Cao","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.31768\/2312-8852.2015.37(3):173-180","article-title":"Application of serex-analysis for identification of human colon cancer antigens","volume":"37","author":"Garifulin","year":"2015","journal-title":"Exp. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12031-019-01369-x","article-title":"Identification of Potential Biomarkers with Diagnostic Value in Pituitary Adenomas Using Prediction Analysis for Microarrays Method","volume":"69","author":"Peng","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.canlet.2004.06.050","article-title":"Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice","volume":"216","author":"Aozuka","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.molmed.2008.06.003","article-title":"The moonlighting enzyme CD13: Old and new functions to target","volume":"14","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104316","DOI":"10.1016\/j.ejmg.2021.104316","article-title":"Cancer predisposition and germline CTNNA1 variants","volume":"64","author":"Lobo","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106302","DOI":"10.1016\/j.phrs.2022.106302","article-title":"Targeting the WASF3 complex to suppress metastasis","volume":"182","author":"Limaye","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2174\/1566524016666160523143937","article-title":"The Role of the PERK\/eIF2\u03b1\/ATF4\/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress","volume":"16","author":"Pytel","year":"2016","journal-title":"Curr. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1074\/jbc.M117.785592","article-title":"An HNF4\u03b1\u2013microRNA-194\/192 signaling axis maintains hepatic cell function","volume":"292","author":"Morimoto","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"956314","DOI":"10.3389\/fgene.2022.956314","article-title":"Comprehensive analysis of karyopherin alpha family expression in lung adenocarcinoma: Association with prognostic value and immune homeostasis","volume":"13","author":"Lan","year":"2022","journal-title":"Front. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fahrmann, J.F., Tanaka, I., Irajizad, E., Mao, X., Dennison, J.B., Murage, E., Casabar, J., Mayo, J., Oeng, Q., and Celiktas, M. (2022). Mutational Activation of the NRF2 Pathway Upregulates Kynureninase Resulting in Tumor Immunosuppression and Poor Outcome in Lung Adenocarcinoma. Cancers, 14.","DOI":"10.3390\/cancers14102543"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1600-0560.2009.01359.x","article-title":"Autophagy in cutaneous malignant melanoma","volume":"37","author":"Lazova","year":"2010","journal-title":"J. Cutan. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s11658-021-00288-3","article-title":"MiR-26b-5p inhibits cell proliferation and EMT by targeting MYCBP in triple-negative breast cancer","volume":"26","author":"Ma","year":"2021","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jconrel.2022.09.029","article-title":"Reshaping hypoxia and silencing CD73 via biomimetic gelatin nanotherapeutics to boost immunotherapy","volume":"351","author":"Yuan","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.parint.2011.07.003","article-title":"Expression of oxysterol binding protein isoforms in opisthorchiasis-associated cholangiocarcinoma: A potential molecular marker for tumor metastasis","volume":"61","author":"Loilome","year":"2012","journal-title":"Parasitol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7854297","DOI":"10.1155\/2022\/7854297","article-title":"The Prognostic Significance and Potential Mechanism of Prolyl 3-Hydroxylase 1 in Hepatocellular Carcinoma","volume":"2022","author":"Li","year":"2022","journal-title":"J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s10863-021-09912-5","article-title":"POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling","volume":"53","author":"Li","year":"2021","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41419-021-04107-7","article-title":"PPFIBP1 induces glioma cell migration and invasion through FAK\/Src\/JNK signaling pathway","volume":"12","author":"Dong","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.21037\/jgo-21-390","article-title":"Increased RBM12 expression predicts poor prognosis in hepatocellular carcinoma based on bioinformatics","volume":"12","author":"Gao","year":"2021","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1111\/1346-8138.16125","article-title":"Increased expression of secreted protein acidic and rich in cysteine and tissue inhibitor of metalloproteinase-3 in epidermotropic melanoma metastasis","volume":"48","author":"Meling","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"679584","DOI":"10.3389\/fmolb.2021.679584","article-title":"Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components","volume":"8","author":"Faoro","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1158\/1535-7163.MCT-06-0083","article-title":"Implications of tissue transglutaminase expression in malignant melanoma","volume":"5","author":"Kok","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1006936","DOI":"10.3389\/fgene.2022.1006936","article-title":"Research progress on the relationship between the TOR signaling pathway regulator; epigenetics; and tumor development","volume":"13","author":"Sun","year":"2022","journal-title":"Front. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Miettinen, J.J., Kumari, R., Traustadottir, G.A., Huppunen, M.-E., Sergeev, P., Majumder, M.M., Schepsky, A., Gudjonsson, T., Lievonen, J., and Bazou, D. (2021). Aminopeptidase Expression in Multiple Myeloma Associates with Disease Progression and Sensitivity to Melflufen. Cancers, 13.","DOI":"10.3390\/cancers13071527"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1046\/j.0022-202x.2001.01657.x","article-title":"Role of Zyxin in Differential Cell Spreading and Proliferation of Melanoma Cells and Melanocytes","volume":"118","author":"Leccia","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41416-019-0641-0","article-title":"Aconitase 2 inhibits the proliferation of MCF-7 cells promoting mitochondrial oxidative metabolism and ROS\/FoxO1-mediated autophagic response","volume":"122","author":"Ciccarone","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1158\/1541-7786.MCR-22-0163","article-title":"Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non-Small Cell Lung Cancer","volume":"21","author":"Mirhadi","year":"2023","journal-title":"Mol. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1021\/acschembio.0c00889","article-title":"Dutomycin Induces Autophagy and Apoptosis by Targeting the Serine Protease Inhibitor SERPINB6","volume":"16","author":"Jang","year":"2021","journal-title":"ACS Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio Cancer Genomics Portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical Profiles Using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"188675","DOI":"10.1016\/j.bbcan.2021.188675","article-title":"Oncosuppressive and oncogenic activity of the sphingolipid-metabolizing enzyme \u03b2-galactosylceramidase","volume":"1877","author":"Belleri","year":"2022","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3389\/fonc.2020.00380","article-title":"GALC Triggers Tumorigenicity of Colorectal Cancer via Senescent Fibroblasts","volume":"10","author":"Yang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3233\/CBM-170995","article-title":"Epithelial-mesenchymal transition and GALC expression of circulating tumor cells indicate metastasis and poor prognosis in non-small cell lung cancer","volume":"22","author":"Liu","year":"2018","journal-title":"Cancer Biomark."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pellerin, L., Carri\u00e9, L., Dufau, C., Nieto, L., S\u00e9gui, B., Levade, T., Riond, J., and Andrieu-Abadie, N. (2020). Lipid metabolic reprogramming: Role in melanoma progression and therapeutic perspectives. Cancers, 12.","DOI":"10.3390\/cancers12113147"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113741","DOI":"10.1016\/j.biopha.2022.113741","article-title":"Endoplasmic reticulum stress in melanoma pathogenesis and resistance","volume":"155","author":"Kong","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Huang, C., Radi, R.H., and Arbiser, J.L. (2021). Mitochondrial metabolism in melanoma. Cells, 10.","DOI":"10.3390\/cells10113197"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lai, M., La Rocca, V., Amato, R., Freer, G., Costa, M., Spezia, P.G., Quaranta, P., Lombardo, G., Piomelli, D., and Pistello, M. (2021). Ablation of acid ceramidase impairs autophagy and mitochondria activity in melanoma cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063247"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106132","DOI":"10.18632\/oncotarget.22190","article-title":"Immune system and melanoma biology: A balance between immunosurveillance and immune escape","volume":"8","author":"Passarelli","year":"2017","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.2217\/imt-2017-0089","article-title":"Sphingolipid pathway enzymes modulate cell fate and immune responses","volume":"9","author":"Molino","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12944-021-01581-y","article-title":"Cell surface sphingomyelin: Key role in cancer initiation; progression; and immune evasion","volume":"20","author":"Tallima","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1158\/2326-6066.CIR-20-0342","article-title":"Neutral sphingomyelinase 2 heightens anti-melanoma immune responses and anti-PD-1 therapy efficacy","volume":"9","author":"Montfort","year":"2021","journal-title":"Cancer Immunol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.1021\/pr9005316","article-title":"The Proapoptotic C16-Ceramide-Dependent Pathway Requires the Death-Promoting Factor Btf in Colon Adenocarcinoma Cells","volume":"8","author":"Leprince","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1021\/pr4003432","article-title":"2\u2032-Hydroxy C16-Ceramide Induces Apoptosis-Associated Proteomic Changes in C6 Glioma Cells","volume":"12","author":"Kota","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1074\/mcp.RA118.001267","article-title":"Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease","volume":"18","author":"Pellegrini","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0009-3084(90)90042-P","article-title":"Synthesis, Spectral Properties and Enzymatic Hydrolysis of Fluorescent Derivatives of Cerebroside Sulfate Containing Long-Wavelength-Emission Probes","volume":"53","author":"Marchesini","year":"1990","journal-title":"Chem. Phys. Lipids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1158\/1535-7163.MCT-13-0487","article-title":"Long Pentraxin-3 Inhibits Epithelial\u2013Mesenchymal Transition in Melanoma Cells","volume":"12","author":"Ronca","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1093\/brain\/awt215","article-title":"Inhibition of Angiogenesis by \u03b2-Galactosylceramidase Deficiency in Globoid Cell Leukodystrophy","volume":"136","author":"Belleri","year":"2013","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19676","DOI":"10.1074\/jbc.M606938200","article-title":"Osteopontin Overexpression Inhibits in Vitro Re-Endothelialization via Integrin Engagement","volume":"282","author":"Leali","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1002\/jcb.25549","article-title":"HMGB1 Osteo-Modulatory Action on Osteosarcoma SaOS-2 Cell Line: An Integrated Study from Biochemical and -Omics Approaches","volume":"117","author":"Martinotti","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jprot.2016.02.021","article-title":"The secretome signature of malignant mesothelioma cell lines","volume":"145","author":"Manfredi","year":"2016","journal-title":"J. Proteomics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/biomet\/93.3.491","article-title":"Adaptive linear step-up procedures that control the false discovery rate","volume":"93","author":"Benjamini","year":"2006","journal-title":"Biometrika"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10555\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:59:27Z","timestamp":1760126367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,23]]},"references-count":60,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310555"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310555","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,23]]}}}