title: Syndecans - key regulators of cell signaling and biological functions.
abstract: Syndecans are a small family of four transmembrane proteoglycans in mammals. They have similar structural organization, consisting of an N-terminal ectodomain, single transmembrane domain and C-terminal cytoplasmic domain. Over the years, the association between syndecans and the actin cytoskeleton has been established, which has consequences for the regulation of cell adhesion and migration. Specifically, ecto- and cytoplasmic domains are responsible for the interaction with extracellular matrix molecules and intracellular kinases, respectively. These interactions indicate syndecans as key molecules during cancer initiation and progression. Particularly syndecans interact with other cell surface receptors, such as growth factor receptors and integrins, which lead to activation of downstream signaling pathways, which are critical for the cellular behavior. Moreover, this review describes the key role of syndecans in intracellular calcium regulation and homeostasis. The syndecan-mediated regulation of calcium metabolism is highly correlated with cells' adhesion phenotype through the actin cytoskeleton and formation of junctions, with implications during differentiation and disease progression.
authors: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Greece.|Biotech Research & Innovation Center, University of Copenhagen, Denmark.
authors: Nikolaos A
authors: NA
authors: Afratis
authors: Laboratory of Anatomy-Histology-Embryology, School of Medicine, University of Crete, Heraklion, Greece.
authors: Dragana
authors: D
authors: Nikitovic
authors: Biotech Research & Innovation Center, University of Copenhagen, Denmark.
authors: Hinke A B
authors: HA
authors: Multhaupt
authors: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Greece.
authors: Achilleas D
authors: AD
authors: Theocharis
authors: Biotech Research & Innovation Center, University of Copenhagen, Denmark.
authors: John R
authors: JR
authors: Couchman
authors: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Greece.
authors: Nikos K
authors: NK
authors: Karamanos
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000072417:Protein Domains; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053667:Syndecans / Q000235:genetics / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D016023:Integrins; D017978:Receptors, Growth Factor; D053667:Syndecans; D011494:Protein Kinases; D002118:Calcium
keywords: cell adhesion; growth factor receptors; growth factors; integrins; migration; signaling; syndecans