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oai:figshare.com:article/33717502 2026-09-14T04:25:30Z category_388 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Secretory carrier membrane protein 3 modulates nuclear ERK1/2 signaling and drug response in triple-negative breast cancer.zip Beatriz M. Morales-Cabán (24867451) Millenia Jackson-González (24867454) Fernando A. Acosta-Pérez (24867457) Bryan S. Ortiz-Torres (24867460) Ivette J. Suárez-Arroyo (6374006) Oncology and Carcinogenesis not elsewhere classified ERK1/2 MK-8353 RAS/RAF SCAMP3 triple-negative breast cancer Introduction<p>Triple-negative breast cancer (TNBC) frequently displays hyperactive mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases 1/2 (ERK1/2) signaling but lacks tractable targets to sustain durable pathway inhibition. Identifying modulators that shape ERK1/2 output and influence responses to ERK1/2 inhibitors is therefore needed. The endosomal trafficking protein secretory carrier membrane protein 3 (SCAMP3) is a positive regulator of epidermal growth factor receptor (EGFR) signaling and ERK1/2-dependent phosphoproteomics programs in TNBC. However, the mechanism by which SCAMP3 modulates ERK1/2 signaling and targeted drug response remains unclear. </p>Methods<p>Here, we combined SCAMP3 knockout with pharmacological ERK1/2 inhibition to evaluate SCAMP3's contributions to MAPK signaling, ERK1/2 distribution, cell-cycle control, apoptosis, and in vivo drug response. </p>Results<p>We found that SCAMP3 expression is upregulated in TNBC models harboring intrinsic MAPK-activating alterations compared with MAPK wild-type breast cancer cells. SCAMP3 knockout reduced RAF-MEK-ERK1/2 signaling, decreased nuclear accumulation of active ERK1/2, arrested the cell cycle, and promoted apoptotic responses. Furthermore, SCAMP3 knockout increased the inhibitory response to the ERK1/2-targeted inhibitor MK-8353 in xenograft models of MAPK wild-type TNBC. </p>Conclusion<p>This study identifies SCAMP3 as an important modulator of ERK1/2 signaling and supports further investigation of SCAMP3 as a potential therapeutic co-target to improve ERK1/2-directed therapies.</p> 2026-09-14T04:25:30Z Dataset Dataset 10.3389/fonc.2026.1854966.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Secretory_carrier_membrane_protein_3_modulates_nuclear_ERK1_2_signaling_and_drug_response_in_triple-negative_breast_cancer_zip/33717502 CC BY 4.0