{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:18:52Z","timestamp":1791875932191,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["202001301"],"award-info":[{"award-number":["202001301"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liquid\u2013liquid phase separation (LLPS) has emerged as a critical mechanism underlying oncogenic signaling and transcriptional regulation; however, its involvement in triple\u2010negative breast cancer (TNBC) remains largely unknown. The pleckstrin homology\u2010like domain family B member 2 (PHLDB2) has been implicated in cytoskeletal organization and cell migration, but its role in phase separation\u2013mediated tumor progression has not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an integrative multi\u2010omics analysis combining transcriptomic profiling, bioinformatic modeling, and molecular biology experiments to elucidate the function of PHLDB2 in TNBC. Expression, mutation, and copy number variation of phase separation\u2013related genes were analyzed using TCGA, METABRIC, and GTEx datasets. PHLDB2 knockdown and overexpression models were established in MDA\u2010MB\u2010231 and HCC38 cells to assess cell proliferation, epithelial\u2013mesenchymal transition (EMT), and extracellular matrix (ECM)\u2013related pathways. Immunofluorescence and fluorescence recovery after photobleaching (FRAP) assays were performed to evaluate the phase separation properties of PHLDB2. In\u00a0vivo, xenograft and pulmonary metastasis models were used to validate the effects of Phldb2 knockdown on TNBC growth and metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PHLDB2 was significantly upregulated in TNBC and correlated with poor clinical prognosis. Gene ontology and KEGG analyses revealed its enrichment in ECM\u2013receptor interaction and focal adhesion pathways. PHLDB2 knockdown inhibited cell proliferation and migration, suppressed EMT by upregulating E\u2010cadherin and downregulating N\u2010cadherin, vimentin, Snail, and MMP\u20102. PONDR analysis identified extensive intrinsically disordered regions (IDRs) within PHLDB2, and FRAP assays confirmed its ability to form dynamic, reversible condensates consistent with LLPS. In\u00a0vivo, Phldb2 depletion markedly reduced tumor growth and pulmonary metastases and prolonged survival in TNBC\u2010bearing mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that PHLDB2 promotes TNBC progression by mediating ECM remodeling and EMT activation through phase separation\u2013driven signal organization. These results establish PHLDB2 as a novel phase separation\u2013dependent oncogenic regulator and highlight its potential as a prognostic biomarker and therapeutic target in TNBC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71308","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T13:57:10Z","timestamp":1764511030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase Separation of\n                    <scp>PHLDB2<\/scp>\n                    Drives\n                    <scp>EMT<\/scp>\n                    and Tumor Progression in Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical 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