Dataset Information

SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Loyda Melendez

LAB HEAD: Loyda M. Melendez

PROVIDER: PXD064784 | Pride | 2025-10-27

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	BeatrizMorales_TMTAnalysis_15Feb2023_Rep.msf	Msf
	BeatrizMorales_TMTAnalysis_15Feb2023_Rep.mzML	Mzml
	BeatrizMorales_TMTAnalysis_15Feb2023_Rep.mzTab	Mztab
	TMT_Pool1_Fraction1_BeatrizMorales_16feb2023.raw	Raw
	TMT_Pool1_Fraction2_BeatrizMorales_16feb2023.raw	Raw

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Publications

SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.

Morales-Cabán Beatriz M BM Cantres-Rosario Yadira M YM Tosado-Rodríguez Eduardo L EL Roche-Lima Abiel A Meléndez Loyda M LM Boukli Nawal M NM Suarez-Arroyo Ivette J IJ

International journal of molecular sciences 20251001 19

Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors show therapeutic potential in triple-negative breast cancer (TNBC), but resistance through compensatory signaling limits their efficacy. We previously identified the secretory carrier membrane protein 3 (SCAMP3) as a regulator of TNBC progression and ERK1/2 activation. Here, we investigated the role of SCAMP3 in ERK1/2 signaling and therapeutic response using TMT-based LC-MS/MS phosphoproteomics of wild-type (WT) and <i>SCAMP3</i> kno ...[more]

PMID: 41096842

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