PXD013926

PXD013926 is an original dataset announced via ProteomeXchange.

Title	Increasing Pexophagy as an Unconventional Mode to Kill Cancer Cells
Description	The autophagy-mediated degradation of peroxisomes, pexophagy, serves as a rheostat for peroxisome homeostasis. However, disturbing this process has yet to be investigated in the context of therapy treatment and resistance in cancer. In Vorinostat (Vor)-resistant lymphoma (B8) cells, an autophagosome enrichment procedure, followed by mass spectrometry (MS), revealed an abundance of peroxisomal proteins, indicative of elevated pexophagy. This was validated by immunofluorescence colocalization and co-immunoprecipitation of PEX5 with the pexophagy receptor p62. Using Vor-resistant B8 cells, we triggered apoptosis by genetically silencing PEX1, PEX6 and PEX26, members of the exportomer complex, which negatively regulates pexophagy. To further explore PEX26 in other model systems, we genetically silenced the exportomer component in A549 (lung adenocarcinoma), 1205Lu (melanoma) and in 1205Lu cells with acquired resistance to MAPK-targeted therapies (VCR5). Here, we observed that silencing PEX26 promotes therapy sensitivity under otherwise therapy-resistant conditions. Using gene expression data from lymphoma (DLBCL), melanoma and lung adenocarcinoma cohorts, we found that low gene expression of PEX26, a component of the “negative regulation of pexophagy” signature, was significantly associated with prolonged patient survival. Clinically, gene expression levels of this signature could be utilized as a prognostic indicator in DLBCL, lung adenocarcinoma, melanoma, and perhaps other cancers. In conclusion, we provide precedence for the development and use of therapies that promote pexophagy in cancer. Furthermore, the MS-based identification of autophagosome cargos provides a platform towards identifying proteins unique to pro-death and pro-survival autophagosomes in cancer model systems, which could illuminate therapeutic use and development.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_08:14:25.392.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francois-Michel Boisvert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-20 03:14:32	ID requested
⏵ 1	2022-08-11 08:14:26	announced

Dahabieh MS, Huang F, Goncalves C, Flores Gonz, á, lez RE, Prabhu S, Bolt A, Di Pietro E, Khoury E, Heath J, Xu ZY, R, é, my-Sarrazin J, Mann KK, Orthwein A, Boisvert FM, Braverman N, Miller WH, Del Rinc, ó, n SV, Silencing PEX26 as an unconventional mode to kill drug-resistant cancer cells and forestall drug resistance. Autophagy, 18(3):540-558(2022) [pubmed]

submitter keyword: Peroxisome, autophagy, pexophagy, cancer, exportomer, metabolism

Sonia V. del Rincón
contact affiliation	Lady Davis Institute, McGill University
contact email	sonia.delrincon@mcgill.ca
lab head
Francois-Michel Boisvert
contact affiliation	Université de Sherbrooke
contact email	fm.boisvert@usherbrooke.ca
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/2022/08/PXD013926

PRIDE project URI

• PRIDE
  1. PXD013926
     1. Label: PRIDE project
     2. Name: Increasing Pexophagy as an Unconventional Mode to Kill Cancer Cells