Anti-CD15 monoclonal antibody, clone Cv39

Aberrant protein fucosylation is associated with cancer malignancy. Fucosyltransferase IV (FUT4) is the key enzyme catalyzing the biosynthesis of alpha 1,3-linkage fucosylated glycans carried by glycoproteins on the cell surface, such as the tumor-associated sugar antigen Lewis Y (LeY). An abnormal increase in the levels of FUT4 and LeY is observed in many cancers and correlated with cell proliferation and metastasis. Some microRNAs (miRNAs) are known to negatively regulate gene expression. FUT4 is an oncogenic glycogene, and thus it is important to identify the specific miRNA targeting FUT4. In current study, we first identified miR-200b as a specific miRNA that inhibited FUT4 expression. We found that miR-200b level was decreased, whereas that of FUT4 was increased in tissues and serum of breast cancer compared with that in the control by real-time PCR, western blotting and enzyme-linked immunosorbent assay. The alterations of miR-200b and FUT4 level were recovered after chemotherapy. The results also showed that miR-200b suppressed FUT4 expression and inhibited tumor growth and metastasis in MCF-7 and MDA-MB-231 breast cancer cells, as well as in the xenografted tumor tissues and metastatic lung tissues. miR-200b decreased the alpha 1,3- fucosylation and LeY biosynthesis on epidermal growth factor receptor (EGFR), as well as inactivation of EGFR and downstream phosphoinositide-3 kinase/Akt signaling pathway. In conclusion, the study highlights that FUT4 could apply as a novel target for miR-200b that suppress the proliferation and metastasis of breast cancer cells by reducing a1,3- fucosylation and LeY biosynthesis of glycoproteins. miR-200b and FUT4 are potential diagnostic and therapeutic targets for breast cancer.

The aim of this study is to assess the expression levels of SMYD2 in human tissue samples and cells of colon cancer, and further explore the potential mechanisms of SMYD2 in colon cancer progression. Quantitative PCR and Immunohistochemical (IHC) assays were performed to detect SMYD2 expression in 76 tissue samples of colon cancer tissues and the corresponding normal tissues. The potential correlations between SMYD2 expression levels and clinical pathological features were assessed. We further detected the effects of SMYD2 on the proliferation, invasion and apoptosis of colon cancer cells and on ERBB2/FUT4 signaling pathway through Brdu assay, transwell assay and flow cytometry assay, respectively. The potential effects of SMYD2 on tumor growth were explored using an animal model. We demonstrated the possible involvement of SMYD2 in the progression of colon cancer. We found the high expression of SMYD2 in human colon cancer tissues and cells, and found the correlations between SMYD2 expression and the clinicopathological features including vascular invasion (P = 0.007*), TNM stage (P = 0.016*) and lymph node metastasis (P = 0.011*), of patients with colon cancer. Our data further confirmed that SMYD2 affects cell proliferation, invasion, and apoptosis of colon cancer cells via the regulation of ERBB2/FUT4 signaling pathway. We also demonstrated SMYD2 contributed to tumor growth of colon cancer cells in vivo. We investigated the potential involvement of SMYD2 in the progression of colon, and therefore confirmed SMYD2 as a possible therapeutic target for colon cancer.