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Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide.
- Source :
-
Cell Chemical Biology . Feb2017, Vol. 24 Issue 2, p149-158. 10p. - Publication Year :
- 2017
-
Abstract
- Summary Although resistance toward small-molecule chemotherapeutics has been well studied, the potential of tumor cells to avoid destruction by membrane-lytic compounds remains unexplored. Anticancer peptides (ACPs) are a class of such agents that disrupt tumor cell membranes through rapid and non-stereospecific mechanisms, encouraging the perception that cellular resistance toward ACPs is unlikely to occur. We demonstrate that eukaryotic cells can, indeed, develop resistance to the model oncolytic peptide SVS-1, which preferentially disrupts the membranes of cancer cells. Utilizing fission yeast as a model organism, we show that ACP resistance is largely controlled through the loss of cell-surface anionic saccharides. A similar mechanism was discovered in mammalian cancer cells where removal of negatively charged sialic acid residues directly transformed SVS-1-sensitive cell lines into resistant phenotypes. These results demonstrate that changes in cell-surface glycosylation play a major role in tumor cell resistance toward oncolytic peptides. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 24519456
- Volume :
- 24
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cell Chemical Biology
- Publication Type :
- Academic Journal
- Accession number :
- 121244727
- Full Text :
- https://doi.org/10.1016/j.chembiol.2016.12.009