Implication of N-acetylglucosaminyltransferases III and V in cancer: gene regulation and signaling mechanism.

N-acetylglucosaminyltransferases III (GnT-III) and V (GnT-V) play a pivotal role in the processing of N-linked glycoproteins, and are highly involved in cancer progression and metastasis. Expression of GnT-III and GnT-V in the liver is enhanced during hepatocarcinogenesis, although they are not expressed in the normal liver. Gene expression of GnT-V is regulated by a transcriptional factor, ets-1, which is involved in angiogenesis and invasion of tumor cells. When the formation of the product of GnT-V, GlcNAc-beta1-6 branches, is inhibited by overexpression of GnT-III, lung metastasis of melanoma cells is suppressed. Modification of glycoprotein receptors such as the receptors for epidermal growth factor and nerve growth factor by GnT-III sense transfection changes an intracellular signaling pathway, which may lead to a variety of biological alterations in tumor cells. In this review, we focus on cancer progression and metastasis in relation to GnT-III and GnT-V.