A cytoplasmic C-terminal fragment of Syndecan-1 is generated by sequential proteolysis and antagonizes Syndecan-1 dependent lung tumor cell migration.

ABSTRACT: Syndecan-1 is a surface expressed heparan sulphate proteoglycan, which is upregulated by several tumor types and involved in tumor cell migration and metastasis. Syndecan-1 is shed from the cell surface and the remaining transmembrane fragment undergoes intramembrane proteolysis by γ-secretase. We here show that this generates a cytoplasmic C-terminal fragment (cCTF). In epithelial lung tumor A549 cells the endogenously produced cCTF accumulated when its proteasomal degradation was blocked with bortezomib and this accumulation was prevented by γ-secretase inhibition. Overexpression of the cCTF suppressed migration and invasion of A549 cells. This inhibitory effect was only seen when endogenous Syndecan-1 was present, but not in Syndecan-1 deficient cells. Further, overexpression of Syndeca

SUBMITTER: Pasqualon T 

PROVIDER: S-EPMC4741606 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature