N-acetylglucosaminyl 1-phosphate transferase: an excellent target for developing new generation breast cancer therapeutic.

Studies from our laboratory have explained that breast tumor progression can be attenuated by targeting the N-linked glycoproteins of the tumor microvasculature and that of tumor cells alike with a protein N-glycosylation inhibitor, tunicamycin. Absence of N-glycosylation leads to an accumulation of un- or mis-folded proteins in the ER and the cell develops “ER stress”. The result is cell cycle arrest, and induction of apoptosis mediated by () signaling. Tunicamycin inhibited and (Matrigel™ implants in athymic nude mice) angiogenesis in a dose dependent manner. The action is irreversible and survived under tumor microenvironment, i.e., in the presence of FGF-2 or VEGF or higher serum concentration. Importantly, tunicamycin prevented the progression of double negative (ER/PR/Her2) and triple negative (ER/PR/Her2) breast tumors by ∼55% - 65% in three weeks in athymic nude mice [Balb/c()]. Analyses of paraffin sections exhibited “ER stress” in both microvasculature and in tumor tissue.