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Simple Summary  Sialylation is a post-translational modification that consists in the addition of sialic acid to growing glycan chains on glycoproteins and glycolipids. Aberrant sialylation is an established hallmark of several types of cancer, including breast, ovarian, pancreatic, prostate, colorectal and lung cancers, melanoma and hepatocellular carcinoma. Hypersialylation can be the effect of increased activity of sialyltransferases and results in an excess of negatively charged sialic acid on the surface of cancer cells. Sialic acid accumulation contributes to tumor progression by several paths, including stimulation of tumor invasion and migration, and enhancing immune evasion and tumor cell survival. In this review we explore the mechanisms by which sialyltransferases promote cancer progression. In addition, we provide insights into the possible use of sialyltransferases as biomarkers for cancer and summarize findings on the development of sialyltransferase inhibitors as potential anti-cancer treatments.    Abstract  Sialylation is an integral part of cellular function, governing many biological processes including cellular recognition, adhesion, molecular trafficking, signal transduction and endocytosis. Sialylation is controlled by the levels and the activities of sialyltransferases on glycoproteins and lipids. Altered gene expression of these enzymes in cancer yields to cancer-specific alterations of glycoprotein sialylation. Mounting evidence indicate that hypersialylation is closely associated with cancer progression and metastatic spread, and can be of prognostic significance in human cancer. Aberrant sialylation is not only a result of cancer, but also a driver of malignant phenotype, directly impacting key processes such as tumor cell dissociation and invasion, cell-cell and cell-matrix interactions, angiogenesis, resistance to apoptosis, and evasion of immune destruction. In this review we provide insights on the impact of sialylation in tumor progression, and outline the possible application of sialyltransferases as cancer biomarkers. We also summarize the most promising findings on the development of sialyltransferase inhibitors as potential anti-cancer treatments.

Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?