OtherPerspective
Open Access

Deciphering the cell surface glyco-code: a promising perspective on unveiling the vulnerability of cancer stem cells

Yuanyan Wei, Anning Wei, Yirong Li, Yuerong Yang, Yu Si, Yi Li, Zhijun Fan and Jianhai Jiang
Cancer Biology & Medicine November 2024, 21 (11) 963-969; DOI: https://doi.org/10.20892/j.issn.2095-3941.2024.0408

Article Figures & Data

Figures

  • The unique glycan chain structures on the surface of CSCs have an important role in maintaining the characteristics of CSCs. (A) The high-mannose type N-glycan of CD133 is necessary for its interaction with DNMT1. The collaboration between CD133 and DNMT1 facilitates the repression of p21 and p27 through a promoter methylation mechanism, thereby enhancing the tumorigenesis of CSCs. (B) The O-linked, core 2 α-2,3 sialoglycan expressed on CD44 promotes its interaction with hyaluronic acid (HA), triggering the recruitment of Src family kinases, which are critical for phosphorylation of various signaling proteins. The downstream consequences of these phosphorylations lead to the activation of STAT3, a transcription factor that, upon dimerization and nuclear translocation, induces the expression of numerous genes, including VEGF, PD-1, and TGF-β. This sequence of events enables CSCs to secrete cytokines and growth factors that suppress immune cell functions, thus evading anti-tumor immune responses. (C) GALNT1 mediates O-linked glycosylation of SHH to promote the activation of sonic hedgehog (SHH) signaling. Upon binding of SHH to the Ptch receptor, a conformational change occurs that alleviates inhibitory control of Ptch over Smo. The release of this inhibition activates Smo, triggering a cascade of signaling events. In the presence of SHH, GLI proteins are converted into the active forms, which then translocate to the nucleus. Within the nucleus, these proteins bind to specific promoter sequences, activating target genes, such as Gli1 and CCND1, which are critical for the self-renewal and maintenance of CSCs (figure generated in Figdraw).
    Figure 1

    The unique glycan chain structures on the surface of CSCs have an important role in maintaining the characteristics of CSCs. (A) The high-mannose type N-glycan of CD133 is necessary for its interaction with DNMT1. The collaboration between CD133 and DNMT1 facilitates the repression of p21 and p27 through a promoter methylation mechanism, thereby enhancing the tumorigenesis of CSCs. (B) The O-linked, core 2 α-2,3 sialoglycan expressed on CD44 promotes its interaction with hyaluronic acid (HA), triggering the recruitment of Src family kinases, which are critical for phosphorylation of various signaling proteins. The downstream consequences of these phosphorylations lead to the activation of STAT3, a transcription factor that, upon dimerization and nuclear translocation, induces the expression of numerous genes, including VEGF, PD-1, and TGF-β. This sequence of events enables CSCs to secrete cytokines and growth factors that suppress immune cell functions, thus evading anti-tumor immune responses. (C) GALNT1 mediates O-linked glycosylation of SHH to promote the activation of sonic hedgehog (SHH) signaling. Upon binding of SHH to the Ptch receptor, a conformational change occurs that alleviates inhibitory control of Ptch over Smo. The release of this inhibition activates Smo, triggering a cascade of signaling events. In the presence of SHH, GLI proteins are converted into the active forms, which then translocate to the nucleus. Within the nucleus, these proteins bind to specific promoter sequences, activating target genes, such as Gli1 and CCND1, which are critical for the self-renewal and maintenance of CSCs (figure generated in Figdraw).

  • Application of glycans in CSC sorting and targeted therapy. Lectins specifically recognize and bind the polysaccharide structures on the CSC surface, facilitating their classification and enrichment. (A) The lectin SLBR-N recognizing α-2,3 sialic acid of the O-glycine chain can promote efficient enrichment of breast cancer stem cells through purification. (B) The purification of CSC is enhanced by the combination of anti-CD133 antibody and CVN lectin that recognizes Manα1,2-Man. (C) Lewis X is a purified and enrichment marker for human GBM stem cells. Moreover, specific polysaccharide chain structure inhibition can significantly reduce the biology of CSCs. (D) Inhibition of fucosylation by 2-deoxy-D-galactose contributes to the eradication of CSCs. (E) Blocking the interaction between Siglec-10 and CD24 by anti-CD24 antibody restores the phagocytosis of cancer cells by macrophages. (F) Interfering with GD3S expression, a key enzyme that affects expression of the breast cancer stem cell marker, GD2, can reduce the CSC population and its associated properties (figure created with BioRender.com).
    Figure 2

    Application of glycans in CSC sorting and targeted therapy. Lectins specifically recognize and bind the polysaccharide structures on the CSC surface, facilitating their classification and enrichment. (A) The lectin SLBR-N recognizing α-2,3 sialic acid of the O-glycine chain can promote efficient enrichment of breast cancer stem cells through purification. (B) The purification of CSC is enhanced by the combination of anti-CD133 antibody and CVN lectin that recognizes Manα1,2-Man. (C) Lewis X is a purified and enrichment marker for human GBM stem cells. Moreover, specific polysaccharide chain structure inhibition can significantly reduce the biology of CSCs. (D) Inhibition of fucosylation by 2-deoxy-D-galactose contributes to the eradication of CSCs. (E) Blocking the interaction between Siglec-10 and CD24 by anti-CD24 antibody restores the phagocytosis of cancer cells by macrophages. (F) Interfering with GD3S expression, a key enzyme that affects expression of the breast cancer stem cell marker, GD2, can reduce the CSC population and its associated properties (figure created with BioRender.com).

  • The glyco-code of CSCs holds great promise as a candidate for clinical diagnostic markers and therapeutic targets. During tumor progression, the glycan structures of CSCs differ from those of non-stem cancer cells. These abnormal glycan structures play crucial roles in immune evasion and metastasis, as well as in maintaining the properties of CSCs and enabling the selection of CSCs through lectin binding. Targeted therapeutic strategies, such as shRNA or pharmacologic inhibitors, can target pathways associated with abnormal glycan structures, providing new strategies for CSC therapy and potential methods to enhance cancer immunotherapy (figure created with BioRender.com).
    Figure 3

    The glyco-code of CSCs holds great promise as a candidate for clinical diagnostic markers and therapeutic targets. During tumor progression, the glycan structures of CSCs differ from those of non-stem cancer cells. These abnormal glycan structures play crucial roles in immune evasion and metastasis, as well as in maintaining the properties of CSCs and enabling the selection of CSCs through lectin binding. Targeted therapeutic strategies, such as shRNA or pharmacologic inhibitors, can target pathways associated with abnormal glycan structures, providing new strategies for CSC therapy and potential methods to enhance cancer immunotherapy (figure created with BioRender.com).

Back to top

In this issue

Print
Download PDF
Email Article
Citation Tools

Jump to section