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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Albuquerque, APB (Author) Other; Balmana, M (Author) Other; Mereiter, S (Author) Other; Pinto, F (Author) Other; Celso Reis (Author) ICBAS; Beltrao, EIC (Author) Other

Journal

Title: Biological Chemistry

Vol. 399

Pages: 661-672

ISSN: 1431-6730

Publisher: Walter De Gruyter

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00R-A86

DOI: 10.1515/hsz-2018-0121

Abstract (EN): 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-1 alpha 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-1a 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12