HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway

Heparan sulfate proteoglycan is a key component of cell microenvironment and plays an important role in cell-cell interaction, adhesion, migration, and signal transduction. Heparan sulfate 3-O-sulfotransferase 1 (HS3ST1) is a metabolic-related gene of HS. The present study was aimed at exploring the role of HS3ST1 in the progress of non-small-cell lung cancer (NSCLC). Our results illustrated that HS3ST1 promoted the malignant behaviors of NSCLC cells both in vitro and in vivo. HS3ST1 was found to inhibit spot-type zinc finger protein (SPOP) expression, which might inhibit the NF-κB pathway activation through mediating the degradation of Fas-associated death domain protein (FADD). By analyzing NSCLC patient samples, we also found increased HS3ST1 expression and decreased SPOP expression in tumor tissues in contrast with those in adjoining normal tissues. In conclusion, HS3ST1 promotes NSCLC tumorigenesis by regulating SPOP/FADD/NF-κB pathway.