Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide

Ken Ishikawa, Scott H. Medina, Joel P. Schneider, Amar J.S. Klar

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalCell Chemical Biology
Volume24
Issue number2
DOIs
StatePublished - Feb 16 2017

Fingerprint

Polysaccharides
Cells
Membranes
Peptides
Tumors
Neoplasms
Cell Membrane
Glycosylation
Schizosaccharomyces
Eukaryotic Cells
N-Acetylneuraminic Acid
Cell membranes
Yeast
Phenotype
Cell Line
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Ishikawa, Ken ; Medina, Scott H. ; Schneider, Joel P. ; Klar, Amar J.S. / Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide. In: Cell Chemical Biology. 2017 ; Vol. 24, No. 2. pp. 149-158.
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Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide. / Ishikawa, Ken; Medina, Scott H.; Schneider, Joel P.; Klar, Amar J.S.

In: Cell Chemical Biology, Vol. 24, No. 2, 16.02.2017, p. 149-158.

Research output: Contribution to journalArticle

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