{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:04:42Z","timestamp":1789362282190,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vivo<\/jats:italic>\n                      drug response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1854966","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:34:20Z","timestamp":1789360460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Secretory carrier membrane protein 3 modulates nuclear ERK1\/2 signaling and drug response in triple-negative breast cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Beatriz M.","family":"Morales-Cab\u00e1n","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Universidad Central del Caribe","place":["Bayam\u00f3n, PR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millenia","family":"Jackson-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Universidad Central del Caribe","place":["Bayam\u00f3n, PR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Acosta-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Industrial and Systems Engineering, University of Wisconsin-","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan S.","family":"Ortiz-Torres","sequence":"additional","affiliation":[{"name":"Department of Industrial and Systems Engineering, University of Wisconsin-","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivette J.","family":"Su\u00e1rez-Arroyo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Universidad Central del Caribe","place":["Bayam\u00f3n, PR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4274\/ejbh.galenos.2025.2024-10-2","article-title":"Prognostic significance and molecular classification of triple negative breast cancer: a systematic review","volume":"21","author":"Dogra","year":"2025","journal-title":"Eur J Breast Health"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1405491","article-title":"Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic 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