6480

ST6GAL1

ST6 beta-galactosamide alpha-2,6-sialyltranferase 1;ST6GAL1;ST6 beta-galactosamide alpha-2,6-sialyltranferase 1

B-cell antigen CD75|CMP-N-acetylneuraminate beta-galactosamide alpha-2,6-sialyltransferase|CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,6-sialyltransferase 1|ST6Gal I|alpha 2,6-ST 1|beta-galactoside alpha-2,6-sialyltransferase 1|sialyltransferase 1

3q27.3

protein-coding

OBJECTIVE: CDw75 is an alpha(2,6)-sialylated antigen associated with a poor prognosis in gastric cancer. In the present study, we examined if CDw75 expression in colorectal cancer (CRC) predicts tumour recurrence. Besides, we evaluated CDw75 expression in different colorectal tissue specimens to clarify their role in tumour development and progression. METHODS: We analyzed CDw75 expression in 34 specimens of healthy disease-free colorectal mucosa, 19 specimens of inflammatory colorectal mucosa, 73 colorectal adenomas, 35 specimens of healthy tissue and 101 specimens of tumoural tissue from CRC patients. RESULTS: None of the healthy disease-free and inflammatory colorectal mucosa specimens showed the presence of the epitope. CDw75 was expressed in 26% of the colorectal adenomas. In healthy and tumoural tissue from CRC patients, CDw75 was detected in 22.9% and 82.2% of the specimens, respectively. CDw75 expression in tumoural tissue was correlated with growth pattern (p = 0.044), Dukes stage (p = 0.002), TNM stage (p = 0.020) and distant metastasis (p = 0.005). Survival analysis showed that CDw75 expression is not associated with tumour recurrence. CONCLUSION: CDw75 expression in CRC is not a prognostic factor for predicting disease-free survival. Nevertheless, CDw75 expression may be a good marker of tumour progression and of the malignant potential of CRC.

BACKGROUND: Previously, we found that beta-galactoside alpha2,6-sialyltransferase (ST6Gal I), an enzyme that adds sialic acids to N-linked oligosaccharides of glycoproteins and is frequently overexpressed in cancer cells, is up-regulated by ionizing radiation (IR) and cleaved to a form possessing catalytic activity comparable to that of the Golgi-localized enzyme. Moreover, this soluble form is secreted into the culture media. Induction of ST6Gal I significantly increased the migration of colon cancer cells via sialylation of integrin beta1. Here, we further investigated the mechanisms underlying ST6Gal I cleavage, solubilization and release from cells, and addressed its functions, focusing primarily on cancer cell migration. METHODS: We performed immunoblotting and lectin affinity assay to analyze the expression of ST6 Gal I and level of sialylated integrin beta1. After ionizing radiation, migration of cells was measured by in vitro migration assay. alpha2, 6 sialylation level of cell surface was analyzed by flow cytometry. Cell culture media were concentrated and then analyzed for soluble ST6Gal I levels using an alpha2, 6 sialyltransferase sandwich ELISA. RESULT: We found that ST6Gal I was cleaved by BACE1 (beta-site amyloid precursor protein-cleaving enzyme), which was specifically overexpressed in response to IR. The soluble form of ST6Gal I, which also has sialyltransferase enzymatic activity, was cleaved from the Golgi membrane and then released into the culture media. Both non-cleaved and cleaved forms of ST6Gal I significantly increased colon cancer cell migration in a sialylation-dependent manner. The pro-migratory effect of the non-cleaved form of ST6Gal I was dependent on integrin beta1 sialylation, whereas that of the cleaved form of ST6Gal I was not, suggesting that other intracellular sialylated molecules apart from cell surface molecules such as integrin beta1 might be involved in mediating the pro-migratory effects of the soluble form of ST6Gal I. Moreover, production of soluble form ST6Gal I by BACE 1 inhibited integrin beta1 sialylation and migration by Golgi-anchored form of ST6Gal I. CONCLUSIONS: Our results suggest that soluble ST6Gal I, possibly in cooperation with the Golgi-bound form, may participate in cancer progression and metastasis prior to being secreted from cancer cells.

Skin tumors have become one of the most common cancers in the world and their carcinogenesis is frequently associated with altered glycosylation patterns. The aberrant sialylation, a type of glycosylation, can mediate pathophysiological key events during various stages of tumor progression, including invasion and metastasis. Sialyltransferases play a key role in a variety of biological processes, including cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. In this study, it was evaluated the expression of ST3Gal I and ST6Gal I in cutaneous epithelial lesions that include actinic keratosis (n=15), keratoacanthoma (n=9), squamous cell carcinoma (n=22) and basal cell carcinoma (n=28) in order to evaluate if sialyltransferases expression is different in premalignant and in malignant tumors. The expression of ST3Gal I was observed in actinic keratosis (53%), keratoacanthoma (78%), squamous cell carcinoma (73%) and basal cell carcinoma (32%) with statistic differences between basal cell carcinoma and keratoacanthoma (P=0.0239) and basal cell carcinoma and squamous cell carcinoma (P=0.0096); for ST6Gal I, cytoplasmic expression was noted in actinic keratosis (40%), heterogeneous and cytoplasmic expression was noted in keratoacanthoma (67%), squamous cell carcinoma (41%) and basal cell carcinoma (7%) with statistic differences between basal cell carcinoma and squamous cell carcinoma (P=0.0061) and basal cell carcinoma and keratoacanthoma (P=0.0008). In summary, our results showed that the high expression of ST3Gal I and ST6Gal I, in skin tumors, is associated with tumors with greater potential for invasion and metastasis, as in the case of squamous cell carcinoma, and this may be related to their behavior.