The heparan sulfate proteoglycan Syndecan-1 regulates colon cancer stem cell function via a focal adhesion kinase - Wnt signaling axis'.

In colon cancer, downregulation of the transmembrane heparan sulfate proteoglycan syndecan-1(Sdc-1) is associated with increased invasiveness, metastasis, and dedifferentiation. Since Sdc-1 modulates signaling pathways relevant to stem cell function, we tested the hypothesis that it may regulate a tumor-initiating cell phenotype. Sdc-1 small-interfering RNA knockdown in the human colon cancer cell lines Caco2 and HT-29 resulted in an increased side population (SP), enhanced aldehyde dehydrogenase 1 activity, and higher expression of CD133, LGR5, EPCAM, NANOG, SRY (sex-determining region Y)-box 2, KLF2, and TCF4/TCF7L2. Sdc-1 knockdown enhanced sphere formation, cell viability, Matrigel invasiveness, and epithelial-to-mesenchymal transition-related gene expression.