{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:36Z","timestamp":1788415956703,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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) is characterized by aggressive behavior and extensive extracellular-matrix remodeling. Type I collagen (COL I), a major stromal component, promotes tumor progression, but the downstream tumor-cell mechanisms remain incompletely defined. We investigated whether COL I regulates acyl-CoA synthetase long-chain family member 5 (ACSL5) through ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1) and whether this relationship contributes to malignant behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated public-dataset analyses, transcriptome sequencing, and in vitro functional and biochemical assays. MDA-MB-231 and BT-549 cells were exposed to COL I, with ACSL5 overexpression or UBE2V1 knockdown as indicated. ACSL5 expression and stability were assessed by qPCR, western blotting, CHX-chase analysis, CQ or MG132 treatment, ubiquitination assays, immunoprecipitation-mass spectrometry, and co-immunoprecipitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>COL I enhanced proliferation, colony formation, migration, and invasion and reduced ACSL5 protein abundance in both TNBC cell lines. ACSL5 overexpression partially reversed these malignant phenotypes. COL I did not significantly alter ACSL5 mRNA expression by qPCR but accelerated ACSL5 protein loss; MG132, but not chloroquine, partially restored ACSL5, and total ACSL5 ubiquitination increased after COL I treatment. Immunoprecipitation-mass spectrometry and co-immunoprecipitation identified UBE2V1 as an ACSL5-associated protein whose expression and association with ACSL5 were enhanced by COL I. UBE2V1 knockdown partially restored ACSL5 protein expression and significantly attenuated COL I-induced migration and invasion. Public-dataset analyses further showed reduced ACSL5 expression in breast cancer and associations between ACSL5 and immune-infiltration features; these observations were exploratory and were not supported by direct immune-functional assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify a COL I-UBE2V1-ACSL5 regulatory relationship that contributes to TNBC malignant progression. The data support UBE2V1-associated regulation of proteasome-sensitive ACSL5 loss, while the complete ubiquitination machinery and the in vivo, clinical, and immune relevance remain to be defined.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1916886","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:01Z","timestamp":1788412501000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I collagen promotes triple-negative breast cancer progression through a UBE2V1\u2013ACSL5 regulatory axis"],"prefix":"10.3389","volume":"16","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oncology, Wuxi Maternity and Child Health Care Hospital, Women\u2019s Hospital of Jiangnan University, Jiangnan University","place":["Wuxi, 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