Related Experiment Video
Updated: Aug 21, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Deglycosylation of SLAMF7 in breast cancers enhances phagocytosis
Shih-Han Wang1, Wen-Cheng Chou1, Hsiang-Chi Huang1
1Institute of Biomedical Sciences, Academia Sinica Taipei 115, Taiwan.
Abstract:
N-linked glycosylation of proteins is one of the post-translational modifications (PTMs) that shield tumor antigens from immune attack. Signaling lymphocytic activation molecule family 7 (SLAMF7) suppresses cancer cell phagocytosis and is an ideal target under clinical development. PTM of SLAMF7, however, remains less understood. In this study, we investigated the role of N-glycans on SLAMF7 in breast cancer progression. We identified seven N-linked glycosylation motifs on SLAMF7, which are majorly occupied by complex structures. Evolutionally conserved N98 residue is enriched with high mannose and sialylated glycans. Hyperglycosylated SLAMF7 was associated with STT3A expression in breast cancer cells. Inhibition of STT3A by a small molecule inhibitor, N-linked glycosylation inhibitor-1 (NGI-1), reduced glycosylation of SLAMF7, resulting in enhancing antibody affinity and phagocytosis. To provide an on-target effect, we developed an antibody-drug conjugate (ADC) by coupling the anti-SLAMF7 antibody with NGI-1. Deglycosylation of SLAMF7 increases antibody recognition and promotes macrophage engulfment of breast cancer cells. Our work suggests deglycosylation by ADC is a potential strategy to enhance the response of immunotherapeutic agents.
Insights
N-linked glycosylation shields tumor antigens like SLAMF7 from immune attack. Inhibiting glycosylation enhances antibody binding and cancer cell phagocytosis, offering a new immunotherapy strategy.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- N-linked glycosylation is a post-translational modification (PTM) that can shield tumor antigens from immune surveillance.
- Signaling lymphocytic activation molecule family 7 (SLAMF7) is a target in cancer therapy, but its PTMs, particularly glycosylation, are not well understood.
Purpose of the Study:
- To investigate the role of N-linked glycans on SLAMF7 in breast cancer progression.
- To explore the therapeutic potential of targeting SLAMF7 glycosylation.
Main Methods:
- Identification and characterization of N-linked glycosylation sites on SLAMF7.
- Analysis of SLAMF7 glycosylation patterns in breast cancer cells.
- Inhibition of glycosylation using N-linked glycosylation inhibitor-1 (NGI-1).
- Development and testing of an anti-SLAMF7 antibody-drug conjugate (ADC) carrying NGI-1.
Main Results:
- Seven N-linked glycosylation motifs were identified on SLAMF7, predominantly occupied by complex glycans.
- The N98 residue is evolutionarily conserved and enriched with high mannose and sialylated glycans.
- Hyperglycosylated SLAMF7 correlated with STT3A expression.
- NGI-1 treatment reduced SLAMF7 glycosylation, enhancing antibody affinity and cancer cell phagocytosis.
- The anti-SLAMF7 ADC demonstrated on-target deglycosylation, increasing antibody recognition and macrophage-mediated cancer cell engulfment.
Conclusions:
- Deglycosylation of SLAMF7 enhances its recognition by antibodies and promotes phagocytosis of breast cancer cells.
- Targeting SLAMF7 glycosylation, particularly through antibody-drug conjugates, represents a promising strategy to improve the efficacy of cancer immunotherapies.
