Syndecans – key regulators of cell signaling and biological functions

• Published in: The FEBS journal 2017-01, Vol.284 (1), p.27-41
• Main Authors: Afratis, Nikolaos A., Nikitovic, Dragana, Multhaupt, Hinke A. B., Theocharis, Achilleas D., Couchman, John R., Karamanos, Nikos K.
• Format: Article
• Language: English
• Subjects: Actin; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - metabolism; Adhesion; Animals; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium homeostasis; Cell Adhesion; Cell adhesion & migration; Cell migration; Cell Movement; Cell surface; Cytoskeleton; Domains; Extracellular matrix; Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Gene Expression Regulation; Growth factor receptors; Growth factors; Homeostasis; Humans; Integrins; Integrins - genetics; Integrins - metabolism; Intracellular; Kinases; Metabolism; migration; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Phenotypes; Protein Domains; Protein Kinases - genetics; Protein Kinases - metabolism; Proteoglycans; Receptors; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Regulators; Signal Transduction; Signaling; Syndecan; syndecans; Syndecans - genetics; Syndecans - metabolism
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.13940

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. The interplay of syndecans with growth factor receptors, integrins and ion channels contributes to the regulation of cell functional properties, morphology and signaling. Syndecans, and especially syndecan‐4, associated with actin cytoskeleton regulate cell migration and adhesion during developmental procedures and tumorigenesis. Pharmacological targeting of syndecans biological actions will be a useful tool for the treatment of several diseases and especially cancer.