The role of fucosyltransferases and E-selectin binding in breast cancer metastasis

Abstract

Breast cancer metastasis is one of the leading causes of death among women. E-selectin, which has come under the focus of cancer metastasis studies, has been shown to play an important role in breast cancer metastasis in vitro, but evidence for E-selectin’s role in vivo has been weak at best. We hypothesized that the lack of conclusive data around E-selectin’s role in vivo has been caused by the utilization of mouse breast cancer cell lines instead of human ones. We decided to study the glycosylation enzymes α1,3 fucosyltransferases (Futs) involved in the synthesis of the E-selectin binding tetrasaccharide, Sialyl Lewis X (SLe\(^{X}\)) in order to provide a novel system for understanding the role of E-selectin in breast cancer metastasis. In this study, we analyze the role of the Futs in E-selectin binding in vitro and metastatic tumor growth in vivo in both human and mouse breast cancer cell lines. Our findings reveal that the overexpression of Futs in MDA-231 cells differentially increase E-selectin binding in vitro and promote metastasis in vivo. These trends in vitro and in vivo do not hold when performed in the mouse breast cancer cell line 4T07. Functional analyses of these Futs reveals that they do not seem increase cell proliferation or migration in vitro. These findings seem to indicate that the Futs and E-selectin play a speciesspecific role in increasing breast cancer metastasis, which could help us create new therapeutic targets.