{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:19:21Z","timestamp":1787941161625,"version":"build-2784847793"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A680114"],"award-info":[{"award-number":["N42A680114"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Strategic Research Fund, Mahidol University","award":["MU-SRF-ST-15B\/67"],"award-info":[{"award-number":["MU-SRF-ST-15B\/67"]}]},{"name":"the Strategic Research Fund, Mahidol University","award":["MU-SRF-ST-15B\/67"],"award-info":[{"award-number":["MU-SRF-ST-15B\/67"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Breast cancer (BC) is the most commonly diagnosed malignancy in women, with triple-negative breast cancer (TNBC) representing the most aggressive subtype that is associated with poor clinical outcomes. Identifying novel biomarkers or therapeutic targets is therefore of great importance. Nectin cell adhesion molecule-2 (NECTIN2) is an immunoglobulin-like glycoprotein involved in cell adhesion and immune regulation that is highly expressed in several cancers but its role in the progression of BC is unclear. Using publicly available data sets, we found that NECTIN2 expression is elevated in BC compared to normal tissues and is associated with poorer recurrence-free survival in TNBC patients. Among TNBC cell lines, MDA-MB-231 cells exhibited the highest expression of NECTIN2 at gene and protein levels, consistent with a more aggressive phenotype. To investigate its functional role, we silenced NECTIN2 in MDA-MB-231 and MDA-MB-468 cells. Relative cell viability was modestly reduced in NECTIN2-depleted MDA-MB-231 cells at later time points, but no significant changes were observed in MDA-MB-468 cells. Interestingly, NECTIN2 depletion significantly reduced migration and invasion in MDA-MB-231 cells, but not in MDA-MB-468 cells. Given this cell line\u2013specific effect, subsequent mechanistic investigations focused on the MDA-MB-231 model. Gene expression profiling suggested a reduction in LIMK1, a regulator of cytoskeletal dynamics and cell motility, following NECTIN2 depletion. Furthermore, ectopic expression of LIMK1 in NECTIN2-deficient MDA-MB-231 cells partially restored migratory capacity and was associated with partial epithelial\u2013mesenchymal transition (EMT)-like changes, including a decrease in E-cadherin and ZO-1, and a higher level of fibronectin and Slug. Collectively, these findings suggest that NECTIN2 contributes to migratory and invasive phenotypes in MDA-MB-231 cells, potentially through LIMK1-associated cytoskeletal remodeling and EMT-related marker changes. However, this mechanism requires further investigation because it appears to be context-dependent and may not be universally applicable across TNBC subtypes.<\/jats:p>","DOI":"10.1371\/journal.pone.0356726","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:46:50Z","timestamp":1787939210000},"page":"e0356726","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["NECTIN2 depletion impairs migration and invasion in MDA-MB-231 breast cancer cells through LIMK1-associated cytoskeletal remodeling"],"prefix":"10.1371","volume":"21","author":[{"given":"Phatchanat","family":"Klaihmon","sequence":"first","affiliation":[{"name":"Mahidol University","place":["Bangkok, Thailand"],"department":["Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital"]},{"name":"Mahidol University","place":["Bangkok, Thailand"],"department":["Molecular Cancer 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