Follistatin-related protein 1 is a novel interacting partner of Syndecan-1 complex, mediating in vivo invasion and proliferation

ABSTRACT: Syndecans are cell surface proteoglycans that are involved in many physiopathological processes. To unveil the known signaling effects of shed Syndecan-1 (SDC1) in oral squamous cell carcinoma (OSCC), we overexpressed SDC1 ectodomain and its bioactive peptide and performed immunoaffinity purification followed by mass spectrometry analysis. Follistatin-related protein 1 (FSTL1) was identified with both overexpressed SDC1 forms, and their interaction was confirmed by the solid-phase binding, dot-blotting, confocal co-immunolocalization and selected reaction monitoring (SRM). We have also identified Activin A (ActA) in the SDC1 and pepSDC1 complexes. To further investigate the cross talk between these proteins, singled or doubled silenced SDC1 and FSTL1 OSCC cells were evaluated in an orthotopic mouse model. Tumor tissues showed an opposite epithelial-mesenchymal transition factors regulation, in which singled shSDC1 tissue showed decreased, while singled shFSTL1 and doubled shSDC1-FSTL1 tissues showed increased mRNA levels compared with the control. By Ki-67 immunoreactivity, shFSTL1 showed a higher proliferation than control, which can be explained by the increase in ActA and its receptors mRNA levels. These findings indicate that SDC1 and FSTL1 coordinate individually these two signaling events, acting more strongly on cell invasion and proliferation, respectively. To translate these effects on patient outcome based on their mRNA expression levels, we demonstrated that patients who have individual expression of SDC1 showed higher experience of metastasis than SDC1 and FSTL1 co-expression. This study underscores for the first time the close relationship between SDC1 and FSTL1, signaling, improving our understanding of the role of syndecan-1 in cancer progression.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tongue Cancer Cell Line, Epithelial Cell, Cell Culture

DISEASE(S): Oral Cavity Cancer

SUBMITTER: Adriana Franco Paes Leme  

LAB HEAD: adriana franco paes leme

PROVIDER: PXD008377 | Pride | 2022-02-28

REPOSITORIES: Pride