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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 399, Issue 7

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Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells

Amanda P.B. Albuquerque
  • Biomarkers in Cancer Research Group (BmC) – Federal University of Pernambuco (UFPE), 50670-901 Recife, Pernambuco, Brazil
  • Department of Biochemistry, Federal University of Pernambuco (UFPE), 50670-901 Recife, Pernambuco, Brazil
  • Other articles by this author:
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/ Meritxell Balmaña
  • Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
  • Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
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/ Stefan Mereiter
  • Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
  • Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
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/ Filipe Pinto
  • Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
  • Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
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/ Celso A. Reis
  • Corresponding author
  • Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
  • Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
  • Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
  • Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
  • Email
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/ Eduardo I.C. Beltrão
  • Corresponding author
  • Biomarkers in Cancer Research Group (BmC) – Federal University of Pernambuco (UFPE), 50670-901 Recife, Pernambuco, Brazil
  • Department of Biochemistry, Federal University of Pernambuco (UFPE), 50670-901 Recife, Pernambuco, Brazil
  • Email
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Published Online: 2018-06-12 | DOI: https://doi.org/10.1515/hsz-2018-0121

Abstract

Triple negative breast cancer (TNBC) is a major global public health problem. The lack of targeted therapy and the elevated mortality evidence the need for better knowledge of the tumor biology. Hypoxia and aberrant glycosylation are associated with advanced stages of malignancy, tumor progression and treatment resistance. Importantly, serum deprivation regulates the invasive phenotype and favors TNBC cell survival. However, in TNBC, the role of hypoxia and serum deprivation in the regulation of glycosylation remains largely unknown. The effects of hypoxia and serum deprivation on the expression of glycosyltransferases and glycan profile were evaluated in the MDA-MB-231 cell line. We showed that the overexpression of HIF-1α was accompanied by acquisition of epithelial-mesenchimal transition features. Significant upregulation of fucosyl- and sialyltransferases involved in the synthesis of tumor-associated carbohydrate antigens was observed together with changes in fucosylation and sialylation detected by Aleuria aurantia lectin and Sambucus nigra agglutinin lectin blots. Bioinformatic analysis further indicated a mechanism by which HIF-1α can regulate ST3GAL6 expression and the relationship within the intrinsic characteristics of TNBC tumors. In conclusion, our results showed the involvement of hypoxia and serum deprivation in glycosylation profile regulation of TNBC cells triggering breast cancer aggressive features and suggesting glycosylation as a potential diagnostic and therapeutic target.

This article offers supplementary material which is provided at the end of the article.

Keywords: cancer cell biology; glycosylation; glycosyltransferases; hypoxia; serum deprivation; triple negative breast cancer

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About the article

Received: 2018-01-15

Accepted: 2018-04-27

Published Online: 2018-06-12

Published in Print: 2018-06-27


Citation Information: Biological Chemistry, Volume 399, Issue 7, Pages 661–672, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2018-0121.

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