title: Syndecan-4 Promotes Epithelial Tumor  Cells Spreading and Regulates the Turnover  of PKCα Activity under Mechanical  Stimulation on the Elastomeric Substrates.
abstract: BACKGROUND
  Heparan sulfate proteoglycans (HSPGs) at the cell surface play an important role in cell adhesion, spreading, formation of focal adhesion complexes (FACs), and sensing mechanical stress. Syndecans are members of the HSPGs family and are highly expressed in various tumor cells. Syndecan-4 (SDC4) is a unique member of syndecans that activates protein kinase C alpha (PKCα). However, syndecan-4 in tumor cells development is not clear when receiving mechanical stress. Aims: Here we investigate the role of syndecan-4 in tumor cells spreading and its downstream kinases under mechanical stimulation.
  
  
  METHODS
  Epithelial tumor cells were seeded onto elastomeric polydimethylsiloxane (PDMS) membranes coated with poly-L-lysine (Pl), fibronectin (Fn), or anti-SDC4 antibody and stretched with a modified pressure-driven cell-stretching (PreCS) device.
  
  
  RESULTS
  When cells received mechanical stimulation, engagement of syndecan-4 promoted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 and PKCα at serine 657. Furthermore, we analyzed the cell contractility marker-myosin light chain 2 (MLC2) in 30 min time courses. The levels of phosphorylated MLC2 at serine19 were augmented through ligations of syndecan-4 but not integrin binding motif (RGD) at 10 min mechanical stimulation and were suppressed at 30 min and this phenomenon was associated with the activity of PKCα.
  
  
  CONCLUSIONS
  Our data demonstrate that syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKCα and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility.
mesh_terms: D000818:Animals; D055910:Antibodies, Immobilized / Q000378:metabolism; D001672:Biocompatible Materials / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004129:Dimethylpolysiloxanes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D040542:Mechanotransduction, Cellular; D051379:Mice; D018994:Myosin Light Chains / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D013314:Stress, Mechanical; D053671:Syndecan-4 / Q000378:metabolism*
chemical_list: D055910:Antibodies, Immobilized; D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; D018994:Myosin Light Chains; D053671:Syndecan-4; C107184:myosin light chain 2; C013830:baysilon; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D024722:Cardiac Myosins