SDC1 Knockdown Suppresses Malignant Phenotypes of Breast Cancer by Modulating the MAPK Signaling Pathway

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Breast cancer remains a leading cause of morbidity and mortality among women worldwide, necessitating in-depth 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-1 (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-qPCR 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-8, 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-PAF effectively reversed the inhibitory effects of SDC1 knockdown on cell proliferation, migration, and angiogenesis. Furthermore, in vivo xenograft models confirmed that SDC1 knockdown suppressed tumor growth and reduced microvessel density, while C16-PAF 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.

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