PXD036227

PXD036227 is an original dataset announced via ProteomeXchange.

Title	Chaperone-mediated autophagy promotes PCa survival during ARPI through selective proteome remodeling
Description	Defining acute stress response mechanisms that mediate prostate cancer (PCa) treatment resistance will help improve therapeutic outcomes of patients treated with androgen receptor pathway inhibition (ARPI). ARPI causes abrupt environmental changes, subjecting PCa cells to acute metabolic stress. We identified the up-regulation of chaperone-mediated autophagy (CMA) in response to acute ARPI stress, which persisted in castration-resistant PCa (CRPC). CMA is a selective protein degradation pathway and a key stress response mechanism up-regulated under several stress stimuli, including metabolic stress. As mediator of selective protein degradation, CMA orchestrates cellular pathway changes mediating the cellular stress response. Broad-spectrum proteomic analysis identified CMA induced proteome remodeling acutely after ARPI stress. CMA sustained PCa growth and survival during ARPI, promoting metabolic reprogramming through the upregulation mTORC1 signaling and pathways associated with PCa biosynthesis and energetics. The upregulation of CMA promotes PCa cell proliferation after ARPI, and emergence of CRPC in-vivo. CMA inhibition compromised PCa metabolism, leading to ATP depletion and profound anti-proliferative effects on PCa cells, enhanced when combined with ARPI. CMA inhibition prevented in-vivo tumour formation, while also re-sensitizing enzalutamide-resistant cell lines in-vitro. The profound anti-proliferative effect of CMA inhibition was attributed to cell cycle arrest mediated through p53 transcriptional repression of E2F target genes. This study established CMA as an acute ARPI stress response mechanism, essential in alleviating ARPI induced metabolic stress to promote PCa growth and survival. CMA plays a critical role in the development of ARPI resistance in PCa.
HostingRepository	PRIDE
AnnounceDate	2023-01-26
AnnouncementXML	Submission_2023-01-26_10:13:12.997.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	NicholasNikesitch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-22 03:56:01	ID requested
⏵ 1	2023-01-26 10:13:13	announced

Dataset with its publication pending

submitter keyword: Prostate,CMA, Enzalutamide

MartinGleave
contact affiliation	Director, Vancouver Prostate Centre Chief Executive Officer, PC-TRiADD Distinguished Professor and Head, Department of Urologic Sciences, UBC BC Leadership Chair in Prostate Cancer Research
contact email	m.gleave@ubc.ca
lab head
NicholasNikesitch
contact affiliation	Vancouver Prostate Centre
contact email	nnikesitch@prostatecentre.com
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/2023/01/PXD036227

PRIDE project URI

• PRIDE
  1. PXD036227
     1. Label: PRIDE project
     2. Name: Chaperone-mediated autophagy promotes PCa survival during ARPI through selective proteome remodeling