The emerging importance of α-L-fucose in human breast cancer: a review

Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into glycoproteins and glycolipids which, in turn, are expressed as part of the malignant phenotype. We have noted that fucose is not simply a bystander molecule, but, in fact, contributes to many of the fundamental oncologic properties of breast cancer cells. Here, we summarize the evidence from us and others that fucose is necessary for key functions of neoplastic progression including hematogenous metastasis, tumor invasion through extracellular matrices including basement membranes and up-regulation of the Notch signaling system, with implications for epithelial-to-mesenchymal transition and activation of breast cancer stem cells. Additionally, certain breast cancer biomarkers are fucose-rich while a well-known marker of breast cancer progression, soluble E-selectin, is a known counter-receptor of fucosylated selectin ligands. We provide illustrative examples and supportive evidence drawn from work with human breast cancer cell lines in vitro as well as clinical studies with human pathologic material. And finally, we discuss evidence that fucose (or its absence) is central to the mechanisms of action of several experimental targeted therapies which may prove useful in breast cancer treatment. We propose that alpha-L-fucose is essential in order to construct first, the malignant and then the metastatic phenotype of many human breast cancers. This knowledge may inform the search for novel treatment approaches in breast cancer.