Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44,FEBS Letters

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Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44
FEBS Letters ( IF 3.0 ) Pub Date : 2021-07-30 , DOI: 10.1002/1873-3468.14169
Weitao Liu ₁ , Zhi Ji ₁ , BingRui Wu ₁ , Sijing Huang ₁ , Qihang Chen ₁ , Xiaoning Chen ₁ , Yuanyan Wei ₁ , Jianhai Jiang ₁

Affiliation

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.

中文翻译：

Siglec-15通过抑制CD44溶酶体降解促进肝癌细胞迁移

唾液酸结合免疫球蛋白样凝集素 15 (Siglec-15) 已被确定为癌症免疫治疗的新潜在靶标。在这里，我们探讨了 Siglec-15 在人肝癌细胞中的作用。在本研究中，我们发现与非肿瘤组织相比，肝癌组织中 Siglec-15 的表达显着上调。在功能上，体外实验表明Siglec-15促进肝癌细胞的迁移。此外，数据证明了 Siglec-15 和 CD44 之间的相互作用，CD44 是一种介导肿瘤进展和转移的跨膜糖蛋白。此外，我们表明 CD44 被肝癌细胞中 N-聚糖上的 α2,6 连接的唾液酸修饰，并且 CD44 唾液酸化影响其与 Siglec-15 的相互作用。从 CD44 中去除唾液酸残基会抑制 Siglec-15 和 CD44 之间的相互作用。我们进一步证明 Siglec-15 通过阻止溶酶体介导的降解来相互作用并促进 CD44 的稳定性。综上所述，我们的研究结果表明 Siglec-15 通过调节 CD44 蛋白的稳定性来促进肝癌细胞的迁移。

更新日期：2021-09-13

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