PXD043779

PXD043779 is an original dataset announced via ProteomeXchange.

Title	Evaluation of the secretome of senescent melanoma cells and the impact of silencing Mfn1 on the senescence-associated secretory phenotype (SASP) by shotgun proteomics analysis.
Description	Cellular senescence is a therapy endpoint in melanoma, and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and an enhanced mitochondrial energy metabolism supports resistance to therapy in melanoma. In a previous report we showed that in melanoma, senescence induced by the DNA methylating agent temozolomide, increases fusion proteins mitofusins 1 and 2. Silencing Mfn1 or Mfn2 expression reduced interleukin-6 secretion by senescent cells. Here we expanded these observations evaluating the secretome of senescent melanoma cells using shotgun proteomics, and explored the impact of silencing Mfn1 on the SASP. A significant increase in proteins reported to reduce the immune response towards the tumor was found in the media of senescent cells. The secretion of several of these immunomodulatory proteins was affected by Mfn1 silencing, among them was galectin-9. In agreement, tumors lacking mitofusin 1 responded better to treatment with the methylating agent dacarbazine, tumor size was reduced and a higher immune cell infiltration was detected in the tumor. Our results highlight mitochondrial dynamic proteins as potential pharmacological targets to modulate the SASP in the context of melanoma treatment.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_10:38:25.200.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alejandro Leyva
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-13 23:21:15	ID requested
⏵ 1	2024-01-26 10:38:27	announced

Tarallo D, Mart, í, nez J, Leyva A, M, ó, naco A, Perroni C, Tassano M, Gambini JP, Cappetta M, Dur, á, n R, Moreno M, Quijano C, Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy. Sci Rep, 14(1):909(2024) [pubmed]

10.1038/s41598-024-51427-7;

submitter keyword: Melanoma, Cellular senescence,Secretome, Shotgun Proteomics, Mitofusins

Rosario Durán
contact affiliation	Analytical Biochemistry and Proteomics Unit, Institut Pasteur de Montevideo and Instituto de Investigaciones Biológicas Clemente Estable
contact email	duran@pasteur.edu.uy
lab head
Alejandro Leyva
contact affiliation	Institut Pasteur de Montevideo
contact email	alejandrolp@pasteur.edu.uy
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/PXD043779

PRIDE project URI

• PRIDE
  1. PXD043779
     1. Label: PRIDE project
     2. Name: Evaluation of the secretome of senescent melanoma cells and the impact of silencing Mfn1 on the senescence-associated secretory phenotype (SASP) by shotgun proteomics analysis.