PXD064784

PXD064784 is an original dataset announced via ProteomeXchange.

Title	SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer
Description	Despite the promise of ERK1/2 pathway inhibitors, their efficacy is often limited by feedback mechanisms and pathway adaptability, emphasizing the need to identify co-regulatory proteins that modulate ERK1/2 signaling. Previously, we identified secretory carrier membrane protein 3 (SCAMP3) as a key driver of TNBC progression and a regulator of ERK1/2 activation. In this study, we investigated the role of SCAMP3 in ERK1/2 signaling networks using Tandem Mass Tag (TMT) LC-MS/MS-based phosphoproteomics in TNBC SUM-149 cells and SCAMP3 knockout models treated with the ERK1/2 inhibitor MK-8353. We identified 4,431 phosphosites and detected alterations in nuclear ERK1/2 substrates (ELF1, ELF4), cytoplasmic feedback regulators (Raf-1, MEK2), metabolic enzymes (PCYT1A), and autophagy-related proteins (OPTN, SQSTM1/p62, and TBC1D5), following SCAMP3 knockout. Western blot analysis of SQSTM1/p62, OPTN, and LC3B validated that ERK inhibition was associated with increased SQSTM1/p62 and LC3B-II levels, implicating impaired autophagy flux. Furthermore, silencing of SCAMP3 also affected phosphorylation events mediated by AKT, mTOR, CDK2, CK2, and PKA. Taken together, our findings position SCAMP3 as a central regulator of ERK1/2 signaling and support its potential as a therapeutic target alone or in combination with ERK1/2 inhibitors for TNBC patients.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:55:17.008.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064784
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Loyda Melendez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-09 09:32:05	ID requested
⏵ 1	2025-10-26 17:55:18	announced

Morales-Cab, á, n BM, Cantres-Rosario YM, Tosado-Rodr, í, guez EL, Roche-Lima A, Mel, é, ndez LM, Boukli NM, Suarez-Arroyo IJ, SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer. Int J Mol Sci, 26(19):(2025) [pubmed]

10.6019/PXD064784;

10.3390/ijms26199577;

submitter keyword: proteomics,SCAMP3

Triple Negative Breast Cancer

ERK1/2

autophagy

AKT/mTOR

Loyda M. Melendez
contact affiliation	Translational Proteomics Center, University of Puerto Rico, Medical Sciences Campus
contact email	lmelendezlab@gmail.com
lab head
Loyda Melendez
contact affiliation	University of Puerto Rico Medical Sciences Campus
contact email	lmelendezlab@gmail.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/2025/10/PXD064784

PRIDE project URI

• PRIDE
  1. PXD064784
     1. Label: PRIDE project
     2. Name: SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer