Anti-FUT4 monoclonal antibody, clone 5F21

Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-beta 1(TGF-beta 1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY-mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.

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.