NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.
Fudan University Shanghai Cancer Center, China.
FEBS Lett. 2019 Apr;593(7):719-731. doi: 10.1002/1873-3468.13358. Epub 2019 Mar 29.
CD133 is a widely used cell surface marker of cancer stem cells that plays an important role in tumor initiation and metastasis. Increasing evidence shows that CD133 is secreted to the extracellular space. However, the underlying mechanisms of CD133 secretion remain largely unknown. In this study, we report that secreted CD133 has a complex-type N-glycosylation and is modified by beta1,6GlcNAc N-glycan. We found that inhibition of CD133 complex-type N-glycosylation by swainsonine does not affect the membrane localization of CD133, but significantly reduces CD133 secretion and promotes its accumulation in early endosomes. Moreover, swainsonine reduces CD133 secretion by reducing its mono-ubiquitination and inhibiting the interaction between CD133 and Tsg101. These findings reveal a new mechanism of glycosylation-dependent secretion of CD133.
CD133 是一种广泛应用于癌症干细胞的细胞表面标志物，它在肿瘤的起始和转移中起着重要作用。越来越多的证据表明，CD133 被分泌到细胞外空间。然而，CD133 分泌的潜在机制在很大程度上仍不清楚。在这项研究中，我们报告分泌的 CD133 具有复杂型 N-糖基化，并被β1,6GlcNAc N-糖基化修饰。我们发现，swainsonine 抑制 CD133 复杂型 N-糖基化并不影响 CD133 的膜定位，但显著降低 CD133 的分泌，并促进其在早期内体中的积累。此外，swainsonine 通过减少 CD133 的单泛素化和抑制 CD133 与 Tsg101 的相互作用来减少 CD133 的分泌。这些发现揭示了 CD133 依赖糖基化分泌的新机制。
