PXD065661

PXD065661 is an original dataset announced via ProteomeXchange.

Title	Semaphorin 5A modulates focal adhesion pathway and lamellipodia formation in melanoma
Description	Introduction Metastatic potential and rising incidence make cutaneous melanoma a major health concern worldwide. Although the therapies currently in use have proven effective, their use is limited by side effects arising and development of drug resistance. For this reason, research for new therapeutic targets and predictive biomarkers is crucial. Semaphorin 5A (SEMA5A) is a member of the Semaphorin family with involvement in cancer biology and neural development. We previously demonstrated that this protein promotes different in vitro melanoma aggressive features. In this work we further investigated the role and the mechanism of action of SEMA5A in melanoma formation and progression. Methods We performed proteomic analysis of stable knockdown SEMA5A human melanoma cells, and in silico analysis to identify cellular pathways modulated by SEMA5A. In vitro clonogenic assay and cell viability assay under different substrate conditions were conducted by using both human and murine melanoma SEMA5A knockdown clones. Western blotting analysis and immunofluorescence have been employed to investigate focal adhesion pathway regulation and lamellipodia formation after SEMA5A depletion. Nocodazole assay was used to evaluate focal adhesion dynamic. Xenograft mouse model of melanoma was used to investigate the effect of SEMA5A depletion in tumor formation and growth. Results Ingenuity pathway analysis showed that SEMA5A effects several different cellular pathways essential for cell viability, cell proliferation, and cytoskeletal dynamics, including focal adhesion and lamellipodia formation. We demonstrated that SEMA5A depletion reduced clonogenic properties and cell viability of cells in both low and high stiffness condition of culture. SEMA5A affected Focal adhesion kinase and Paxillin phosphorylation, integrin beta 1 activation, thus regulating focal adhesion dynamics, and lamellipodia formation, regulating Arp3 nucleation and expression. Delay of tumor formation and reduced tumor growth was observed in mice bearing tumor expressing low level of SEMA5A. Conclusions These findings demonstrate that SEMA5A is a novel player of melanoma aggressiveness and progression, being involved in modulating cell viability, focal adhesion signaling and lamellipodia in vitro and tumor growth in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-12-01
AnnouncementXML	Submission_2025-11-30_16:11:11.609.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Concetta Cufaro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-01 08:39:02	ID requested
⏵ 1	2025-11-30 16:11:12	announced

Brignone M, Cufaro MC, Ercolani C, Masi I, Di Ferdinando F, Palange A, Valentini E, Di Martile M, Del Boccio P, Del Bufalo D, Tamagnone L, Rosan, ò L, D'Aguanno S, Semaphorin 5A modulates focal adhesion pathway and lamellipodia formation in melanoma. Cell Commun Signal, 23(1):510(2025) [pubmed]

10.1186/s12964-025-02526-z;

submitter keyword: Semaphorin 5A, melanoma, lamellipodia, focal adhesion

Piero Del Boccio
contact affiliation	Department of Science, University of Chieti, Italy
contact email	piero.delboccio@unich.it
lab head
Maria Concetta Cufaro
contact affiliation	University "G. d'Annunzio" of Chieti
contact email	maria.cufaro@unich.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/2025/12/PXD065661

PRIDE project URI

• PRIDE
  1. PXD065661
     1. Label: PRIDE project
     2. Name: Semaphorin 5A modulates focal adhesion pathway and lamellipodia formation in melanoma