O-glcnacylation Of Functional Proteins Enhanced Migration And Reduced Expression Of E-cadherin In Ovarian Cancer Cells

Ovarian cancer is a common gynecological malignancies and itsmainly clinical treatment are surgical treatment and chemotherapy, but dueto lack of specific indicators of early diagnosis, many patients diagnosedwith distant metastasis, resulting in the most mortality rate in gynecologicalmalignancy, postoperative easy to relapse. So, it is the key to the clinicaltreatment of ovarian cancer that search for the molecular target foreffectively inhibiting invasion and metastasis of ovarian cancer.O-GlcNAcylation is a dynamic protein posttranslationalmodifi cation. The addition of O-GlcNAc to proteins is catalyzedby O-linked-β-N-acetylglucosamine transferase(OGT) and itsremoval is catalyzed by O-GlcNAcase(OGA). Studies have shownthat O-GlcNAcylation plays an important role in the occurrence,development, metastasis and invasion of a variety of tumors, but the role ofO-GlcNAcylation in ovarian cancer metastasis remains unclear. In thisstudy, we modeled diverse ovarian cancer cells to investigate the effect andmolecular mechanism of O-GlcNAcylation on ovarian cancer cell migration.In our study, We found that OGT mRNA and O-GlcNAc wereboth elevated in high-metastatic ovarian cancer HO-8910PM cellscompared to low-metastatic OVCAR3cells. The results suggestedthat O-GlcNAcylation may be involved in regulating ovarian cancer cellmigration. By qPCR and western blot, we detected that O-GlcNAc wasincreased in OVCAR3cells treated by PUG or TMG and reduced inHO-8910PM cells infected with OGT-siRNA. Meanwhile, the migrationwas enhanced in OVCAR3cells treated by PUG or TMG and reduced inHO-8910PM cells infected with OGT-siRNA by transwell assays. We alsofound that expression of E-cadherin and formation of E-cadherin/catenincomplex were reduced in PUG or TMG treated OVCAR3cells andincreased in OGT-siRNA infected HO-8910PM cells. In addition, wedetected that E-cadherin, β-catenin and p120were O-GlcNAcylated. Insummary, our results demonstrate that O-GlcNAcylation could enhanceovarian cancer cell migration and reduce expression of E-cadherin. It alsosuggest that O-GlcNAcylation might become another targ etfor th e t her apy o f ov ari an can cer.