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Abstract
Melanoma is an aggressive skin cancer; an early detection of the primary tumor may improve its prognosis. Despite many genes have been shown to be involved in melanoma, the full framework of melanoma transformation has not been completely explored. The characterization of pathways involved in tumor restraint in in vitro models may help to identify oncotarget genes. We therefore aimed to probe novel oncotargets through an integrated approach involving proteomic, gene expression and bioinformatic analysisWe investigated molecular modulations in melanoma cells treated with ascorbic acid, which is known to inhibit cancer growth at high concentrations. For this purpose a proteomic approach was applied. A deeper insight into ascorbic acid anticancer activity was achieved; the discovery of deregulated processes suggested further biomarkers. In addition, we evaluated the expression of identified genes as well as the migration ability in several melanoma cell lines.Data obtained by a multidisciplinary approach demonstrated the involvement of Enolase 1 (ENO1), Parkinsonism-associated deglycase (PARK7), Prostaglansin E synthase 3 (PTGES3), Nucleophosmin (NPM1), Stathmin 1 (STMN1) genes in cell transformation and identified Single stranded DNA binding protein 1 (SSBP1) as a possible onco-suppressor in melanoma cancer.
Highlights
Malignant melanoma (MM) has been considered a rare cancer for a long time
With the aims of: i) identifying oncotargets and ii) studying proteome variations involved in an antitumor activity, we investigated the pathways modulated by ascorbic acid (AsA) in melanoma cells [3]
The strongest separation was observed in the first and second PCs, which accounted for most of the variation in the data sets, i.e. 22.6% and 19.2% respectively. These results indicate that natural variation in the proteomes is sufficient to allow discrimination between different groups, increasing the confidence that potential disease biomarkers and oncotargets can be found in this dataset
Summary
Malignant melanoma (MM) has been considered a rare cancer for a long time. in the last years incidence of MM has increased considerably in consequence of lifestyle and environmental changes. Many studies, performed in animal models and in primary tumors, shed light on the complex genomic background involved in metastatic progression of MM; it has been reported that mutation rate and gene modulation in melanoma are higher than in other solid malignancies [1, 2]. With the aims of: i) identifying oncotargets and ii) studying proteome variations involved in an antitumor activity, we investigated the pathways modulated by ascorbic acid (AsA) in melanoma cells [3]. It has been demonstrated in vitro that AsA reduces the malignant potential [4, 5] in a murine melanoma model [6] as well as in human melanoma [3]
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