Syndecan-2 positively regulates Wnt/β-catenin signaling in breast cancer cells

Article Article scientifique Article Syndecan-2 positively regulates Wnt/β-catenin signaling in breast cancer cells eng 2025-08-25 2025-11 author Naraghi Leyli Department of Cell and Molecular Biology, School of Biology, College of Sciences, University of Tehran, Tehran P.O.Box 14155-6455, Iran; Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 983961 author Koval Alexey 0000-0002-8920-4426 Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 910996 Département de physiologie cellulaire et métabolisme (PHYME) author Katanaev Vladimir 0000-0002-7909-5617 Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Vladimir.Katanaev@unige.ch. 910192 Département de physiologie cellulaire et métabolisme (PHYME) author A Najafi S Mahmoud Department of Cell and Molecular Biology, School of Biology, College of Sciences, University of Tehran, Tehran P.O.Box 14155-6455, Iran. Electronic address: smarabnajafi@ut.ac.ir. 106853 10.1016/j.biocel.2025.106853 40865674 1357-2725 https://www.sciencedirect.com/science/article/pii/S1357272525001219 Syndecans are a family of four-member transmembrane heparan sulfate proteoglycans that bind to various extracellular biomolecules, such as Wnt ligands, via their heparan sulfate chains, thereby controlling a variety of cellular processes. When dysregulated, syndecans can affect tumorigenesis and cancer progression by modulating key signaling pathways involved in the regulation of biological functions. Aberrant activation of Wnt/β-catenin signaling is a hallmark of many human tumors, including breast cancer. Studying the interplay between syndecans and Wnt signaling in human cancers is beneficial for identifying new therapeutic strategies, understanding tumor behavior and improving patient outcomes. Syndecan-2 is predominantly expressed by mesenchymal cells, and its overexpression in tumors of epithelial origin appears to induce aggressive behavior. Here, by measuring β-catenin cytoplasmic stabilization and transcriptional activity, we show that syndecan-2 expression significantly enhances the sensitivity of HEK293T cells and BT-20 triple-negative breast cancer cells to Wnt3a-induced activation of Wnt/β-catenin signaling. In addition, CRISPR/Cas9-mediated deletion of SDC2, the gene encoding syndecan-2, reduced β-catenin transcriptional activity in BT-20 cells in response to Wnt3a stimulation. This reduction was rescued by the re-expression of SDC2. Collectively, our results demonstrate that syndecan-2 is a positive regulator of canonical Wnt signaling. These results also suggest that syndecan-2 is a potential clinical target for inhibiting the progression of some human cancers. BT-20 CRISPR-Cas9 Heparan sulfate proteoglycan Syndecan-2 Triple-negative breast cancer Wnt/β-catenin signaling Humans Syndecan-2 / metabolism Syndecan-2 / genetics Wnt Signaling Pathway Female HEK293 Cells Beta Catenin / metabolism Beta Catenin / genetics Breast Neoplasms / metabolism Breast Neoplasms / pathology Breast Neoplasms / genetics Cell Line, Tumor Gene Expression Regulation, Neoplastic Wnt3A Protein / metabolism Dewey 612 134 Département de physiologie cellulaire et métabolisme 21C false 1264 Voies de signalisation oncogéniques 998 International journal of biochemistry & cell biology 188 d629dddc-4e9c-482b-be48-a8ef907ba012 Article (Published version) Restricted International_Journal_of_Biochemist.pdf 3594446 application/pdf 7af36d921bcc26f057dc833bd414f5407e64e0cf4965e40e240e6cc88f1b530c c3a158a5-ea21-4c50-a0bb-e2ed68220671 Supplemental data Restricted 1-s2.0-S1357272525001219-mmc1.pdf 632597 application/pdf 40d684f3fac665e8324741aa3cabdaff1e14737e30d0c94839d60aca9be16b05 restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Syndecan-2 positively regulates Wnt/β-catenin signaling in breast cancer cells	International journal of biochemistry & cell biology			2025	40	0

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Naraghi, Leyli