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Biochemical Roles of Eukaryotic Cell Surface Macromolecules pp 355–374Cite as

N-Acetylglucosaminyl 1-Phosphate Transferase: An Excellent Target for Developing New Generation Breast Cancer Therapeutic

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 842))

Abstract

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 unfolded protein response (upr) signaling. Tunicamycin inhibited in vitro and in vivo (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 to 65 % in 3 weeks in athymic nude mice [Balb/c(nu/nu)]. Analyses of paraffin sections exhibited “ER stress” in both microvasculature and in tumor tissue.

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Acknowledgement

The work was supported in whole or in part, by grants from Susan G. Komen for the Cure BCTR0600582 (to D.K.B.) and NIH/NIMHD 2G12MD007583 (to K.B.)

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Author notes

  1. Aditi Banerjee

    Present address: Department of Pediatrics, School of Medicine, University of Maryland, Baltimore, MD, 21202, USA

Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, 00936-5067, USA

    Aditi Banerjee, Juan A. Martinez, Zhenbo Zhang, Jesus Santiago & Dipak K. Banerjee

  2. Department of Chemistry and Physics, Purdue University Calumet Hammond, Hammond, IN, 46323-2094, USA

    Maria O. Longas

  3. Department of Anatomy and Cell Biology, School of Medicine, Universidad Central del Caribe, Bayamon, PR, 00960-3001, USA

    Krishna Baksi

  4. Institute of Functional Nanomaterials, University of Puerto Rico-Rio Piedras, San Juan, PR, 00931-1907, USA

    Dipak K. Banerjee

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  1. Aditi Banerjee
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Correspondence to Dipak K. Banerjee .

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Editors and Affiliations

  1. Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India

    Abhijit Chakrabarti

  2. Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, India

    Avadhesha Surolia

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Banerjee, A. et al. (2015). N-Acetylglucosaminyl 1-Phosphate Transferase: An Excellent Target for Developing New Generation Breast Cancer Therapeutic. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_22

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