c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer.

Abstract

FUT1 is a key rate-limiting enzyme in the synthesis of Lewis y, a membrane-associated carbohydrate antigen. The aberrant upregulation of FUT1 and Lewis y antigen is related to proliferation, invasion and prognosis in malignant epithelial tumors. A c-Fos/activator protein-1 (AP-1) binding site was found in the FUT1 promoter. However, the mechanisms of transcriptional regulation of FUT1 remain poorly understood. TGF-β1 is positively correlated to Lewis y. In the present study, we investigated the molecular mechanism of FUT1 gene expression in response to TGF-β1. We demonstrated that c-Fos was highly expressed in 77.50% of ovarian epithelial carcinoma cases and was significantly correlated with Lewis y. Using luciferase activity and chromatin immunoprecipitation (ChIP) assay, we further revealed that c-Fos interacted with the FUT1 promoter in ovarian cancer cells and transcriptional capacity of the heterodimer formed by c-Fos and c-Jun was stronger than that of the c-Fos or c-Jun homodimers. Then, we demonstrated that TGF-β1 induced dose-dependent c-Fos expression, which was involved in TGF-β1-induced ovarian cancer cell proliferation. In addition, inhibition of MAPK activation or TGF-β1 receptor by pharmacological agents prevented TGF-β1-induced c-Fos and Lewis y expression. Silencing of c-Fos prevented TGF-β1-induced Lewis y expression. Collectively, the results of these studies demonstrated that TGF-β1 regulated FUT1 and Lewis y expression by activating the MAPK/c-Fos pathway.

• Authors: Yingying Hao, Liancheng Zhu, Limei Yan, Juanjuan Liu, Dawo Liu, Na Gao, Mingzi Tan, Song Gao, Bei Lin
• Journal: Oncology reports (Oncol Rep) Vol. 38 Issue 6 Pg. 3355-3366 (Dec 2017) ISSN: 1791-2431 [Electronic] Greece
• PMID: 29130097 (Publication Type: Journal Article)

Chemical References

• Lewis Blood Group Antigens
• Lewis Y antigen
• Proto-Oncogene Proteins c-fos
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Fucosyltransferases

Topics

• Adolescent
• Adult
• Aged
• Binding Sites
• Cell Line, Tumor
• Cell Proliferation
• Female
• Fucosyltransferases (genetics, metabolism)
• Humans
• Lewis Blood Group Antigens (metabolism)
• MAP Kinase Signaling System
• Middle Aged
• Ovarian Neoplasms (genetics, metabolism)
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-fos (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Up-Regulation
• Young Adult
• Galactoside 2-alpha-L-fucosyltransferase