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ST8SIA6 Sialylates CD24 to Enhance Its Membrane Localization in BRCA
Jinxia He1,2, Fengchao Zhang1,2, Baihai Wu1,2
1Key Laboratory of Marine Drugs (Ministry of Education), Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Insights
CD24 protein is highly expressed in breast tumors, correlating with shorter survival. ST8SIA6 promotes CD24 cell membrane localization, revealing a novel mechanism in cancer progression.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- CD24 is a cell surface protein involved in innate immunity, inflammation, and cancer.
- Subcellular localization and sialylation of CD24 in cancer are not well understood.
- The prognostic impact of CD24 expression and localization in cancer is debated.
Purpose of the Study:
- To investigate the pan-cancer expression of CD24 and its clinical correlation.
- To explore the role of sialylation in CD24 subcellular localization.
- To identify the specific sialyltransferase responsible for CD24 modification.
Main Methods:
- Systematic pan-cancer analysis of CD24 gene expression.
- Correlation analysis between CD24 and sialyltransferases (STs).
- Experimental validation of ST8SIA6's role in CD24 sialylation and localization.
Main Results:
- CD24 is highly expressed in breast tumors, associated with decreased patient survival.
- This survival correlation was not observed in other cancer types.
- ST8SIA6 was identified as the key ST regulating CD24 sialylation and promoting cell membrane localization.
Conclusions:
- ST8SIA6 directly modifies CD24, influencing its subcellular localization.
- This study provides the first mechanistic insight into ST8SIA6-mediated CD24 regulation.
- Findings offer new perspectives on CD24's biological roles and therapeutic potential in cancer.
Abstract:
CD24, a highly sialylated glycosyl-phosphatidyl-inositol (GPI) cell surface protein that interacts with sialic acid-binding immunoglobulin-like lectins (Siglecs), serves as an innate immune checkpoint and plays a crucial role in inflammatory diseases and tumor progression. Recently, cytoplasmic CD24 has been observed in samples from patients with cancer. However, whether sialylation governs the subcellular localization of CD24 in cancer remains unclear, and the impact of CD24 expression and localization on the clinical prognosis of cancer remains controversial. Here, we performed a systematic pan-cancer analysis of the gene expression levels and clinical correlation of CD24. Our analysis revealed that CD24 was highly expressed in breast tumor tissues and tumor cells, significantly shortening patient survival time. However, this correlation was not evident in other types of cancer. Additionally, a correlation analysis of CD24 levels with sialyltransferases (STs) revealed that ST8SIA6 is the key ST affecting CD24 sialylation. Further investigation demonstrated that ST8SIA6 directly modified CD24, promoting its localization to the cell membrane. Taken together, these findings elucidate, for the first time, the mechanisms by which ST8SIA6 regulates CD24 subcellular localization, providing new insights into the biological functions and applications of CD24.
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