[Frontiers in Bioscience E4, 499-515, January 1, 2012]

Sialyltransferases functions in cancers

Anne Harduin-Lepers1, Marie-Ange Krzewinski-Recchi1, Florent Colomb1, Francois Foulquier1, Sophie Groux-Degroote1, Philippe Delannoy1

1Univ Lille Nord de France, F-59000 Lille, France, USTL, UGSF, IFR 147, F-59650 Villeneuve d'Ascq, France, CNRS UMR 8576, F-59650 Villeneuve d'Ascq, France


1. Abstract
2. Introduction
3. Human ST involved in the synthesis of sialylated TACA
3.1. The β-galactoside α2,3-sialyltransferases (ST3Gal)
3.2. The β-galactoside α2,6-sialyltransferases (ST6Gal)
3.3. The GalNAc α2,6-sialyltransferasses (ST6GalNAc)
3.4. The α2,8-sialyltransferases (ST8Sia)
4. Investigation-tools to study sialylation changes and STs in cancer
4.1. Linkage and sialylated products formed: Use of lectins and antibodies
4.2. ST enzymatic activities and ST mRNAs: Use of enzymatic assays, Q-PCR, microarrays
4.3. Use of chemical inhibitors of ST activities and ST antisense oligodeoxynucleotides
5. Mechanisms of ST regulation
5.1. Genetic regulation: transcriptional regulation of ST
5.2. Epigenetic regulation
5.3. Post-translational modifications and Golgi pH influence on ST intracellular location and activity
6. Conclusion
7. Acknowledgements
8. References


Abnormally elevated levels of sialylated tumor associated carbohydrate antigens are frequently described at the surface of cancer cells and/or secreted in biological fluids. It is now well established that this over-expression may result from deregulation in sialyltransferases enzymatic activity involved in their biosynthesis, but the precise molecular mechanisms remain unknown. Twenty different human sialyltransferases preside to the sialylation of glycoconjugates, either glycolipids or glycoproteins. This review summarizes the current knowledge on human sialyltransferases implicated in the altered expression of sialylated tumor associated antigens, the molecular basis of their regulated expression in cancer cells and the various tools developed by researchers and clinicians for their study in pathological samples.