Siglec‐15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44

• Published in: FEBS letters Vol. 595; no. 17; pp. 2290 - 2302
• Main Authors: Liu, Weitao, Ji, Zhi, Wu, BingRui, Huang, Sijing, Chen, Qihang, Chen, Xiaoning, Wei, Yuanyan, Jiang, Jianhai
• Format: Journal Article
• Language: English
• Published: 01.09.2021
• Subjects: CD44; migration; Sialic acids; Siglec‐15
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14169

Sialic acid‐binding immunoglobulin‐like lectin‐15 (Siglec‐15) has been identified as a novel potential target for cancer immunotherapy. Here, we explored the role of Siglec‐15 in human hepatoma cells. In this study, we found that the expression of Siglec‐15 is substantially upregulated in liver cancer tissues in comparison with the nontumor tissues. Functionally, in vitro experiments show that Siglec‐15 promotes the migration of hepatoma cells. Furthermore, the data demonstrated an interaction between Siglec‐15 and CD44, a transmembrane glycoprotein that mediates tumor progression and metastasis. In addition, we show that CD44 is modified by α2,6‐linked sialic acids on N‐glycans in hepatoma cells and that CD44 sialylation affects its interaction with Siglec‐15. Removal of the sialic acid residues from CD44 resulted in suppressed interaction between Siglec‐15 and CD44. We further demonstrate that Siglec‐15 interacts and promotes the stability of CD44 by preventing its lysosomal‐mediated degradation. Taken together, our findings demonstrate that Siglec‐15 promotes the migration of hepatoma cells by regulating the CD44 protein stability.