PXD037551

PXD037551 is an original dataset announced via ProteomeXchange.

Title	Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness
Description	Mucosal 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.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:55:32.494.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-19 02:46:56	ID requested
⏵ 1	2024-01-26 06:55:34	announced

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;

submitter keyword: mucosal melanomas, proteomics, cancer cell lines, pre-clinical models, cell line-derived xenografts, melanosomes

Marcello Manfredi
contact affiliation	Biological 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 email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD037551

PRIDE project URI

• PRIDE
  1. PXD037551
     1. Label: PRIDE project
     2. Name: Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness