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PXD037551

PXD037551 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNovel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness
DescriptionMucosal 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. By morphology, ultrastructure and phenotype analysis, this study reports the validation and functional characterization of five cell lines obtained from human melanomas arising from the sino-nasal mucosa and designated as SN-MM1-5. 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 in NOD/SCID mice. 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 on clinical samples. 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. Accordingly, Akt activation, as measured by pAkt(Ser473) and pAkt(Thr308), was observed in all SN-MM and resulted constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3 . A functional role for PI3K-Akt-mTOR pathway was confirmed by PI3K chemical inhibitor LY294002 which significantly impaired SN-MM cell lines viability. Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the immunobiology of these neoplasms and, as extension, to MM from other sites.
HostingRepositoryPRIDE
AnnounceDate2024-01-26
AnnouncementXMLSubmission_2024-01-26_06:55:32.494.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarcello Manfredi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-10-19 02:46:56ID requested
12024-01-26 06:55:34announced
Publication List
Monti M, Benerini Gatta L, Bugatti M, Pezzali I, Picinoli S, Manfredi M, Lavazza A, Vanella VV, De Giorgis V, Zanatta L, Missale F, Lonardi S, Zanetti B, Bozzoni G, Cadei M, Abate A, Vergani B, Balzarini P, Battocchio S, Facco C, Turri-Zanoni M, Castelnuovo P, Nicolai P, Fonsatti E, Leone BE, Marengo E, Sigala S, Ronca R, Perego M, Lombardi D, Vermi W, Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness. J Transl Med, 22(1):35(2024) [pubmed]
10.1186/s12967-023-04784-2;
Keyword List
submitter keyword: mucosal melanomas, proteomics, cancer cell lines, pre-clinical models, cell line-derived xenografts, melanosomes
Contact List
Marcello Manfredi
contact affiliationBiological Mass Spectrometry Lab, Department of Translational Medicine (DiMeT), Center for Translational Research on Autoimmune & Allergic Diseases - CAAD - University of Piemonte Orientale, Corso Trieste 15/A, 28100, Novara, Italy
contact emailmarcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliationUniversity of Eastern Piedmont
contact emailmarcello.manfredi@uniupo.it
dataset submitter
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Dataset FTP location
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