Banford Samantha, Timson David J
University of Brighton School of Pharmacy and Biomolecular Sciences, Brighton, United Kingdom.
Curr Cancer Drug Targets. 2017;17(1):53-61. doi: 10.2174/1568009616666160922102641.
UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer. Abnormally glycosylated forms of mucin 1 (a substrate of the enzyme), are used clinically as a biomarker for breast cancer. There is potential for other products of the pp-GalNAc- T6 catalyzed reaction to be used. It is also possible that pp-GalNAc-T6 itself could be used as a biomarker, since levels of this protein tend to be low in non-malignant tissues. pp- GalNAc-T6 has been implicated in malignant transformation and metastasis of cancer cells. As such, it has considerable potential as a target for chemotherapy. To date, no selective inhibitors of the enzyme have been identified. However, general inhibitors of the enzyme family result in reduced cell surface O-linked glycosylation and induce apoptosis in cultured cells. Thus, a selective inhibitor of pp-GalNAc-T6 is likely to target cancer cells and could be developed into a novel anticancer therapy.
UDP-N-乙酰-D-半乳糖胺：多肽N-乙酰半乳糖胺基转移酶-6（pp-GalNAc-T6）是N-乙酰-D-半乳糖胺转移酶家族的成员。它催化将N-乙酰-D-半乳糖胺添加到蛋白质上，这通常是蛋白质O-糖基化的第一步。糖基化蛋白质在细胞膜的体内发挥重要作用。这些通常参与细胞间粘附、细胞骨架调节和免疫识别。已证明pp-GalNAc-T6在多种癌症类型中上调。粘蛋白1（该酶的一种底物）的异常糖基化形式在临床上用作乳腺癌的生物标志物。pp-GalNAc-T6催化反应的其他产物也有被利用的潜力。pp-GalNAc-T6本身也有可能用作生物标志物，因为该蛋白在非恶性组织中的水平往往较低。pp-GalNAc-T6与癌细胞的恶性转化和转移有关。因此，它作为化疗靶点具有相当大的潜力。迄今为止，尚未鉴定出该酶的选择性抑制剂。然而，该酶家族的通用抑制剂会导致细胞表面O-连接糖基化减少，并在培养细胞中诱导凋亡。因此，pp-GalNAc-T6的选择性抑制剂可能靶向癌细胞，并可开发成一种新型抗癌疗法。
