ArticleJournal of translational medicine2024
Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Comprehensive genomic profiling of mucosal melanoma reveals novel fusion transcripts and dysregulation of cell-cycle, MAPK, and PI3K pathways.The Journal of pathology · 2026Article
- Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas.Journal for immunotherapy of cancer · 2026Article
- Modeling rare melanoma subtypes: mechanisms, microenvironments and translational opportunities.Frontiers in oncology · 2026Review
- Review
- The Roles of PTEN in Melanoma Suppression.Pigment cell & melanoma research · 2025Review
- Specific oncogene activation of the cell of origin in mucosal melanoma.Nature communications · 2025Article
- Capacity for Compensatory Cyclin D2 Response Confers Trametinib Resistance in Canine Mucosal Melanoma.Cancers · 2025Article
- Capacity for compensatory cyclin D2 response confers trametinib resistance in canine mucosal melanoma.bioRxiv : the preprint server for biology · 2025Article
- The microbiome as a therapeutic co-driver in melanoma immuno-oncology.Frontiers in medicine · 2025Review
- Lycopene inhibits ER stress and apoptosis while modulating PI3K/AKT and enhancing antioxidant and anti-apoptotic proteins.PloS one · 2025Article
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Authors and funding
31 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundMucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology.
methodsFive novel cell lines were obtained from patient-derived biopsies of MM arising in the sino-nasal mucosa and designated as SN-MM1-5. The morphology, ultrastructure and melanocytic identity of SN-MM cell lines were validated by transmission electron microscopy and immunohistochemistry. Moreover, in vivo tumorigenicity of SN-MM1-5 was tested by subcutaneous injection in NOD/SCID mice. Molecular characterization of SN-MM cell lines was performed by a mass-spectrometry proteomic approach, and their sensitivity to PI3K chemical inhibitor LY294002 was validated by Akt activation, measured by pAkt(Ser473) and pAkt(Thr308) in immunoblots, and MTS assay.
resultsThis study reports the validation and functional characterization of five newly generated SN-MM cell lines. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo and display recurrent structural variants according to aCGH analysis. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2 + /ZEB1 + /CD271 + cells, supporting the existence of melanoma-initiating cells also in MM, as confirmed in clinical samples. In vitro, SN-MM cell lines were sensitive to cisplatin, but not to temozolomide. Moreover, the proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Consistently, phosphorylation of NDRG1 and Akt activation was observed in SN-MM, the latter being constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3. The cell viability impairment induced by LY294002 confirmed a functional role for the PI3K-Akt-mTOR pathway in SN-MM cell lines.
conclusionsOverall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the biology of these neoplasms and, as an extension, to MM from other sites.
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