N-glycosylation of GSTO1 promotes cervical cancer migration and invasion through JAK/STAT3 pathway activation

Background Protein glycosylation is strongly associated with tumor progression. Glutathione S-transferase omega 1 (GSTO1) is a member of the glutathione S-transferase family. The significance of GSTO1 N-glycosylation in the progression of cervical cancer (CC) has remained elusive. In this study, we investigated the functional significance of GSTO1 N-glycosylation in CC progression. Methods We employed immunohistochemistry to detect the relative expression of evaluating the link between GSTO1 in CC and benign tissues and the overall survival (OS) and progression-free survival (PFS) in CC patients. In vitro and in vivo experiments to detect CC cell proliferation or metastatic ability after GSTO1 downregulation. NetNGly1.0 Server database predicts potential N-glycosylation modification sites of GSTO1 (Asn55, Asn135, Asn190). Investigating GSTO1 N-glycosylation's function in cellular migration, invasion and epithelial–mesenchymal transition (EMT), we mutated the N-glycosylation sites of GSTO1 through lentivirus-based insertional mutagenesis. Detection of signalling pathways associated with N-glycosylation-modified GSTO1 by enrichment analysis and Western blot. Results Compared to normal cervical tissue, CC tissue showed significantly higher GSTO1 expression. Further, high GSTO1 levels were a poor predictor of OS and PFS. Both cell and animal experiments suggested that down-regulation of GSTO1 inhibited cell proliferation and metastasis. Glycosylation modification of targeted mutant GSTO1 at positions 55, 135 and 190 significantly inhibits migration and invasion of CC cells. GSTO1 N-glycosylation fixed point mutation inhibits EMT process in CC cells. Mechanistically, N-glycosylated GSTO1 promoted the expression of JAK/STAT3 pathway related markers. Conclusions GSTO1 N-glycosylation is associated with CC progression and may promote EMT via JAK/STAT3 signaling.