{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyndecan‐4 (SDC4) is emerging as a key regulator of extracellular matrix (ECM) integrity through its control of proteolytic activity and ectodomain shedding. In degenerative joint and disc diseases, SDC4 is up‐regulated in chondrocytes and nucleus pulposus cells, where it directly interacts with metalloproteinases (such as ADAMTS‐5) to enhance proteoglycan degradation and cartilage breakdown. At the same time, in endothelial cells, inflammatory mediators stimulate MMP‐ or ADAM‐dependent shedding of SDC4, which compromises glycocalyx integrity and alters cell–matrix interactions. These studies collectively demonstrate that SDC4 is a critical node in ECM remodeling under inflammatory conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSDC4 also functions as a versatile co‐receptor for growth factors and ECM ligands to orchestrate cell adhesion and signaling. By participating in fibroblast growth factor 2 (FGF2) signaling—through receptor clustering and translocation into specialized membrane microdomains—SDC4 engages intracellular effectors such as protein kinase Cα (PKCα) to promote cell spreading, migration, and proliferation. Moreover, its physical interactions with ADAM12, tenascin‐C–derived peptides, and components of the fibronectin matrix further potentiate adhesive responses. These diverse interactions underscore the role of SDC4 in fine‐tuning growth factor– and matrix‐mediated signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond growth factor signaling, SDC4 is a central mediator of integrin cooperation and mechanotransduction. Its cytoplasmic domain, which binds focal adhesion components such as α‐actinin, and the inherent propensity of its transmembrane segment to oligomerize (a property further reinforced by its lipid interactions) are essential for focal adhesion assembly. Such molecular organization enables cells to sense mechanical cues—including shear stress and matrix tension—and to modulate cytoskeletal dynamics, cell alignment, and ECM contraction. In turn, these biophysical responses drive integrin complex formation and even the development of “catch‐bond” behavior under tension."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its adhesive and mechanical functions, SDC4 plays an important role in immune regulation. Its engagement by molecules such as antithrombin attenuates chemokine‐driven migration of neutrophils, monocytes, and lymphocytes, thereby modulating inflammatory responses. Furthermore, interactions with inhibitory receptors like DC‐HIL on activated T cells contribute to the dampening of T cell activation. Together, these findings highlight SDC4 as an intrinsic negative regulator of immune cell migration and activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSDC4 is also indispensable for cardiovascular homeostasis and cardiac adaptation. In vascular endothelia, it facilitates alignment in the direction of blood flow, acting as a mechanosensor that limits atherosclerotic plaque formation. In the myocardium, SDC4 is required for the activation of calcineurin–NFAT signaling in response to mechanical stress, thereby ensuring compensatory hypertrophy during pressure overload—mechanisms that are critical to maintaining cardiac function under stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAltered expression and regulation of SDC4 are likewise implicated in cancer progression. In breast carcinomas and other tumor types, aberrant SDC4 levels correlate with receptor status and invasive behavior. Through its modulation by growth factor and Wnt signaling pathways and its contribution to integrin‐dependent adhesion, SDC4 influences tumor cell migration, ECM remodeling, and ultimately metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent findings also reveal a non‐canonical role for SDC4 in cytokinesis. By directly coupling to the ESCRT machinery at the midbody, SDC4 facilitates the final abscission step during cell division, thereby securing successful cytokinesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Juan Carlos Rodríguez-Manzaneque, Darren Carpizo, María del Carmen Plaza-Calonge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2008.08.014"}], "href": "https://doi.org/10.1016/j.biocel.2008.08.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18775505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18775505"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Frank Echtermeyer, Jessica Bertrand, Rita Dreier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.1998"}], "href": "https://doi.org/10.1038/nm.1998"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19684582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19684582"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jessica Pruessmeyer, Christian Martin, Franz M Hess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A disintegrin and metalloproteinase 17 (ADAM17) mediates inflammation-induced shedding of syndecan-1 and -4 by lung epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.059394"}], "href": "https://doi.org/10.1074/jbc.M109.059394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19875451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19875451"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jianru Wang, Dessislava Markova, D Greg Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.264549"}], "href": "https://doi.org/10.1074/jbc.M111.264549"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21949132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21949132"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Raina Ramnath, Rebecca R Foster, Yan Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor α: a contributor to endothelial cell glycocalyx dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.14-252221"}], "href": "https://doi.org/10.1096/fj.14-252221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25122554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25122554"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eugene Tkachenko, Michael Simons "}, {"type": "b", "children": [{"type": "t", "text": "Clustering induces redistribution of syndecan-4 core protein into raft membrane domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200841200"}], "href": "https://doi.org/10.1074/jbc.M200841200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11889131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11889131"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Arie Horowitz, Eugene Tkachenko, Michael Simons "}, {"type": "b", "children": [{"type": "t", "text": "Fibroblast growth factor-specific modulation of cellular response by syndecan-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200112145"}], "href": "https://doi.org/10.1083/jcb.200112145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12011116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12011116"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Charles Kumar Thodeti, Reidar Albrechtsen, Morten Grauslund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M208937200"}], "href": "https://doi.org/10.1074/jbc.M208937200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509413"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bernhard H Rauch, Esther Millette, Richard D Kenagy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 is required for thrombin-induced migration and proliferation in human vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410848200"}], "href": "https://doi.org/10.1074/jbc.M410848200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15731100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15731100"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "James R Whiteford, Volker Behrends, Hishani Kirby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecans promote integrin-mediated adhesion of mesenchymal cells in two distinct pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.08.002"}], "href": "https://doi.org/10.1016/j.yexcr.2007.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17870067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17870067"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sara Santana Nunes, Marianna A Ferrari do Outeiro-Bernstein, Luiz Juliano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 contributes to endothelial tubulogenesis through interactions with two motifs inside the pro-angiogenic N-terminal domain of thrombospondin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.21281"}], "href": "https://doi.org/10.1002/jcp.21281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17879962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17879962"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yohei Saito, Hisae Imazeki, Shogo Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A peptide derived from tenascin-C induces beta1 integrin activation through syndecan-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M705608200"}], "href": "https://doi.org/10.1074/jbc.M705608200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17901052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17901052"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Dilek Telci, Zhuo Wang, Xiaoling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta1 integrin co-signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801763200"}], "href": "https://doi.org/10.1074/jbc.M801763200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18499669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18499669"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zhuo Wang, Russell J Collighan, Stephane R Gross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 α5β1 integrin co-signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.123703"}], "href": "https://doi.org/10.1074/jbc.M110.123703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20929862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20929862"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Z Wang, D Telci, M Griffin "}, {"type": "b", "children": [{"type": "t", "text": "Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.10.015"}], "href": "https://doi.org/10.1016/j.yexcr.2010.10.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21036168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21036168"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sonia Carulli, Konrad Beck, Guila Dayan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell surface proteoglycans syndecan-1 and -4 bind overlapping but distinct sites in laminin α3 LG45 protein domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.300061"}], "href": "https://doi.org/10.1074/jbc.M111.300061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22351752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22351752"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Daniel K Greene, Sarka Tumova, John R Couchman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 associates with alpha-actinin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207123200"}], "href": "https://doi.org/10.1074/jbc.M207123200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12493766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12493766"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jennifer A Peterson, Nader Sheibani, Guido David, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparin II domain of fibronectin uses alpha4beta1 integrin to control focal adhesion and stress fiber formation, independent of syndecan-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406625200"}], "href": "https://doi.org/10.1074/jbc.M406625200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15572366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15572366"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sungmun Choi, Eunjung Lee, Soojin Kwon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane domain-induced oligomerization is crucial for the functions of syndecan-2 and syndecan-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M509238200"}], "href": "https://doi.org/10.1074/jbc.M509238200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16253987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16253987"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ian C Dews, Kevin R Mackenzie "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0708909105"}], "href": "https://doi.org/10.1073/pnas.0708909105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18093920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18093920"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "E Okina, T Manon-Jensen, J R Whiteford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan proteoglycan contributions to cytoskeletal organization and contractility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Scand J Med Sci Sports (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0838.2009.00941.x"}], "href": "https://doi.org/10.1111/j.1600-0838.2009.00941.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19538537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19538537"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Vincent F Fiore, Lining Ju, Yunfeng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic catch of a Thy-1-α5β1+syndecan-4 trimolecular complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms5886"}], "href": "https://doi.org/10.1038/ncomms5886"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25216363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25216363"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1413725111"}], "href": "https://doi.org/10.1073/pnas.1413725111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25404299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25404299"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Haiyao Wang, Haining Jin, Alan C Rapraeger "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-1 and Syndecan-4 Capture Epidermal Growth Factor Receptor Family Members and the α3β1 Integrin Via Binding Sites in Their Ectodomains: NOVEL SYNSTATINS PREVENT KINASE CAPTURE AND INHIBIT α6β4-INTEGRIN-DEPENDENT EPITHELIAL CELL MOTILITY."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.679084"}], "href": "https://doi.org/10.1074/jbc.M115.679084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26350464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26350464"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Antonios Chronopoulos, Stephen D Thorpe, Ernesto Cortes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Mater (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41563-019-0567-1"}], "href": "https://doi.org/10.1038/s41563-019-0567-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31907416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31907416"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "N C Kaneider, P Egger, S Dunzendorfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 as antithrombin receptor of human neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2001.5534"}], "href": "https://doi.org/10.1006/bbrc.2001.5534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11549250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11549250"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Nicole C Kaneider, Christina M Reinisch, Stefan Dunzendorfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.115.1.227"}], "href": "https://doi.org/10.1242/jcs.115.1.227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11801740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11801740"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Morgan Hamon, Elisabeth Mbemba, Nathalie Charnaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A syndecan-4/CXCR4 complex expressed on human primary lymphocytes and macrophages and HeLa cell line binds the CXC chemokine stromal cell-derived factor-1 (SDF-1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwh038"}], "href": "https://doi.org/10.1093/glycob/cwh038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15033938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15033938"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Nathalie Charnaux, Séverine Brule, Morgan Hamon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 is a signaling molecule for stromal cell-derived factor-1 (SDF-1)/ CXCL12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2005.04624.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2005.04624.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15819887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15819887"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Trini Teixé, Patricia Nieto-Blanco, Ramon Vilella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-2 and -4 expressed on activated primary human CD4+ lymphocytes can regulate T cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2008.01.033"}], "href": "https://doi.org/10.1016/j.molimm.2008.01.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18342939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18342939"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jin-Sung Chung, Makoto Bonkobara, Mizuki Tomihari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DC-HIL/syndecan-4 pathway inhibits human allogeneic T-cell responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200838990"}], "href": "https://doi.org/10.1002/eji.200838990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19350579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19350579"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Alexandra V Finsen, Ida G Lunde, Ivar Sjaastad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0028302"}], "href": "https://doi.org/10.1371/journal.pone.0028302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22164265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22164265"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Mari E Strand, Kate M Herum, Zaheer A Rana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan-4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure-overloaded heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.12161"}], "href": "https://doi.org/10.1111/febs.12161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23374111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23374111"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Füsun Baba, Kathryn Swartz, Regina van Buren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res Treat (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10549-005-9135-2"}], "href": "https://doi.org/10.1007/s10549-005-9135-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16636895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16636895"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Faten Charni, Veronique Friand, Oualid Haddad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-1 and syndecan-4 are involved in RANTES/CCL5-induced migration and invasion of human hepatoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2009.07.015"}], "href": "https://doi.org/10.1016/j.bbagen.2009.07.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19632304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19632304"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Michael P O'Connell, Jennifer L Fiori, Emily K Kershner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulfate proteoglycan modulation of Wnt5A signal transduction in metastatic melanoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.028498"}], "href": "https://doi.org/10.1074/jbc.M109.028498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19696445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19696445"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "D Marzioni, T Lorenzi, R Mazzucchelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of basic fibroblast growth factor, its receptors and syndecans in bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Immunopathol Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/039463200902200308"}], "href": "https://doi.org/10.1177/039463200902200308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19822079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19822079"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Loreto Carvallo, Rosana Muñoz, Francisco Bustos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-canonical Wnt signaling induces ubiquitination and degradation of Syndecan4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.155812"}], "href": "https://doi.org/10.1074/jbc.M110.155812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20639201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20639201"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Karoliina Vuoriluoto, Gunilla Högnäs, Pipsa Meller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.matbio.2011.03.003"}], "href": "https://doi.org/10.1016/j.matbio.2011.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21414405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21414405"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Maria E Lendorf, Tina Manon-Jensen, Pauliina Kronqvist, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-1 and syndecan-4 are independent indicators in breast carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Histochem Cytochem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1369/0022155411405057"}], "href": "https://doi.org/10.1369/0022155411405057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21430259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21430259"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Merve Erdem, Selcuk Erdem, Oner Sanli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of TGM2 with ITGB1 and SDC4 is important in the development and metastasis of renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urol Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.urolonc.2012.08.022"}], "href": "https://doi.org/10.1016/j.urolonc.2012.08.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23499501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23499501"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Arye Elfenbein, Anthony Lanahan, Theresa X Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan 4 regulates FGFR1 signaling in endothelial cells by directing macropinocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2002495"}], "href": "https://doi.org/10.1126/scisignal.2002495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22569333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22569333"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Cyril Addi, Adrien Presle, Stéphane Frémont, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-15205-z"}], "href": "https://doi.org/10.1038/s41467-020-15205-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32321914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32321914"}]}]}]}