August 15, 2025Open Access

Targeting and Suppression of Survivin in Cancer Cells Based on the Interaction of Cell Surface Vimentin with N-Acetylglucosamine-Bearing Polymers

Key Points

Low-molecular-weight GlcNAc polymers effectively downregulated survivin, enhancing cancer cell sensitivity to treatment.
Experiment with various polymer lengths showed that smaller GlcNAc polymers targeted cancer cells better than larger ones.
Observational analysis using mouse and human cancer cell lines revealed significant decreases in cell viability after treatment.
Findings indicate that targeting vimentin with GlcNAc polymers may improve cancer therapy outcomes, particularly in drug-resistant cases.

Abstract

Survivin, a protein overexpressed in various fetal and malignant tumor tissues, induces tumor progression and resistance to cancer therapy. Cell surface vimentin has N-acetylglucosamine (GlcNAc)-binding activities in several cell types including tumor cells. Furthermore, GlcNAc-bearing polymers downregulate the expression of the survivin-encoding baculoviral inhibitor of apoptosis protein repeat-containing protein 5 (BIRC5). Thus, cell surface vimentin is a target for cancer therapy. The downregulation of survivin expression in cancer cells by selectively targeting cell surface vimentin with GlcNAc-bearing polymers may mitigate drug resistance. However, the ability of GlcNAc to bind to cell surface vimentin depends on its valency in GlcNAc-bearing polymers. The optimal GlcNAc valency for the interaction remains unknown. Therefore, we aimed to develop optimal GlcNAc-bearing polymers for effective cancer therapy. In this study, GlcNAc polymers of various lengths were synthesized through reversible addition/fragmentation chain-transfer polymerization. We found that a low-molecular-weight GlcNAc polymer (5 GlcNAc-mer) interacted with cell surface vimentin-expressing cells to a greater extent than high-molecular-weight GlcNAc polymers (10 and 20 GlcNAc-mer). These interactions upregulated the expression of p53, an upstream signal transducer. Moreover, they inhibited the phosphorylation of signal transducers and activators of transcription 3 and downregulated survivin expression. In addition, low-molecular-weight GlcNAc polymers decreased the viability of 3LL cells, mouse lung carcinoma cell lines, and MCF-7 cells, human breast cancer lines, but not that of MCF10A, nontumorigenic breast cells. These findings suggest that low-molecular-weight GlcNAc polymers, which selectively target cancer cells and downregulate survivin expression, are promising tools for cancer therapy.

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