Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer.

Sialyltransferases transfer sialic acid to nascent oligosaccharides and are upregulated in cancer. The inhibition of sialyltransferases is emerging as a potential strategy to prevent metastasis in several cancers, including ovarian cancer. ST3GAL1 is a sialyltransferase that catalyzes the transfer of sialic acid from cytidine monophosphate-sialic acid to galactose-containing substrates and is associated with cancer progression and chemoresistance. However, the function of ST3GAL1 in ovarian cancer is uncertain. Herein, we use qRT-PCR, western blotting, and immunohistochemistry to assess the expression of ST3GAL1 in ovarian cancer tissue and cell lines and investigate whether it influences resistance to paclitaxel in vitro and in a mouse xenograft model. We found that ST3GAL1 is upregulated in ovarian cancer tissues and in the ovarian cancer cell lines SKOV-3 and OVCAR3 but downregulated in A2780 ovarian cancer cells. Overexpression of ST3GAL1 in A2780 cells increases cell growth, migration, and invasion whereas ST3GAL1 knockdown in SKOV-3 cells decreases cell growth, migration, and invasion. Furthermore, overexpression of ST3GAL1 increases resistance to paclitaxel while downregulation of ST3GAL1 decreases resistance to paclitaxel in vitro, and overexpression of ST3GAL1 increases tumorigenicity and resistance to paclitaxel in vivo. Transforming growth factor-β1 can increase ST3GAL1 expression and induce ovarian cell epithelial-mesenchymal transition (EMT). However, knockdown of ST3GAL1 inhibits EMT expression. Taken together, our findings have identified a regulatory mechanism involving ST3GAL1 in ovarian cancer. ST3GAL1 may be a promising target for overcoming paclitaxel resistance in ovarian carcinoma.