{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:29:20Z","timestamp":1786418960868,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Breast cancer remains a leading cause of morbidity and mortality among women worldwide, necessitating in\u2010depth research into its molecular mechanisms to improve prognosis and treatment strategies. This study investigates the expression profile and functional role of heparan sulfate proteoglycan Syndecan\u20101 (SDC1) in breast cancer progression, with a focus on its downstream signaling pathways. Utilizing bioinformatics analysis of datasets from the GEO and TCGA databases, we identified significantly elevated SDC1 expression in breast cancer tissues compared to normal counterparts, correlating with advanced tumor stage, lymph node metastasis, and poor survival outcomes. Clinical sample validation through RT\u2010qPCR and Western blot confirmed SDC1 overexpression in breast cancer tissues and cell lines. Functional experiments, including SDC1 knockdown via lentiviral infection, revealed that reduced SDC1 expression markedly impairs breast cancer cell proliferation, migration, and angiogenesis, as evidenced by CCK\u20108, EdU, wound healing, Transwell, and tube formation assays. Mechanistically, transcriptome sequencing and Western blot analysis demonstrated that SDC1 knockdown significantly suppressed the phosphorylation of key MAPK pathway components (ERK1\/2, JNK, and p38). Rescue experiments using the MAPK agonist C16\u2010PAF effectively reversed the inhibitory effects of SDC1 knockdown on cell proliferation, migration, and angiogenesis. Furthermore, in\u00a0vivo xenograft models confirmed that SDC1 knockdown suppressed tumor growth and reduced microvessel density, while C16\u2010PAF treatment partially reversed these effects. Collectively, our findings demonstrate that SDC1 promotes breast cancer progression by activating the MAPK signaling pathway, highlighting SDC1 as a potential prognostic biomarker and therapeutic target in breast cancer.<\/jats:p>","DOI":"10.1002\/cam4.72016","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:41:47Z","timestamp":1782790907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SDC1<\/scp>\n                    Knockdown Suppresses Malignant Phenotypes of Breast Cancer by Modulating the\n                    <scp>MAPK<\/scp>\n                    Signaling Pathway"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9476-0566","authenticated-orcid":false,"given":"Weixun","family":"Lin","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Jinan University  Guangzhou Guangdong People's Republic of China"},{"name":"Department of Thyroid, Breast and Hernia Surgery The Second Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology People's Hospital of Chenghai Shantou  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Thyroid, Breast and Hernia Surgery The Second Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thyroid, Breast and Hernia Surgery The Second Affiliated Hospital of Shantou University Medical College  Shantou Guangdong 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