PXD050029-1

PXD050029 is an original dataset announced via ProteomeXchange.

Title	PTPN23 downregulation by WDR4 Determines the Exosome Secretion Fate of MVB to Promote Cancer Metastasis and Immune Evasion
Description	Exosomes play pleiotropic tumor-promoting functions and are originated from a diversion of endocytic pathway. In late endocytic trafficking, multivesicular bodies (MVBs) are directed to lysosomes for degradation or secreted as exosomes. However, the mechanism controlling different fates of MVBs remains elusive. Here, we show that WDR4 promotes exosome secretion through the degradation of PTPN23, an ESCRT-associated Bro1-family protein. Mechanistically, PTPN23 competes with ALIX, another Bro1-family protein, for binding syntenin, thus enabling PTPN23 and ALIX for promoting MVBs towards degradation and secretion, respectively. Furthermore, ALIX uniquely recruits actin-capping/severing proteins to prevent F-actin accumulation around MVBs, thereby facilitating MVBs trafficking to cell periphery for secretion. Functionally, the WDR4/ALIX-dependent exosomes preferentially load pro-tumor proteins including PTK2, MCAM and NRP1, thereby enhancing metastasis and immune evasion. This study highlights a previously unprecedented mechanism for regulating MVBs fates and exosome cargos, which have potential broad impacts on tuning exosome production and devising cancer therapeutic strategy.
HostingRepository	PRIDE
AnnounceDate	2025-01-24
AnnouncementXML	Submission_2025-01-23_18:27:27.902.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nai-Yang Yeat
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-22 03:43:29	ID requested
⏵ 1	2025-01-23 18:27:28	announced

Dataset with its publication pending

submitter keyword: Ubiquitination, Endocytic trafficking, Actin remodeling,NSCLC, Extracellular Vesicles, Immune checkpoint, Immune evasion, Exosome secretion, Exosome, Cancer metastasis, EVs, Lysosomal degradation

Ruey-Hwa Chen
contact affiliation	Academia Sinica, Institute of Biological Chemistry
contact email	rhchen@gate.sinica.edu.tw
lab head
Nai-Yang Yeat
contact affiliation	Academia Sinica
contact email	naiyang1997@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050029
     1. Label: PRIDE project
     2. Name: PTPN23 downregulation by WDR4 Determines the Exosome Secretion Fate of MVB to Promote Cancer Metastasis and Immune Evasion