C1QBP 在 CSF-1 依赖性 PKCζ 激活和巨噬细胞迁移中的作用。

The role of C1QBP in CSF-1-dependent PKCζ activation and macrophage migration.

机构信息

Department of Urology, Tianjin Medical University Second Hospital, Tianjin Institute of Urology, Tianjin Medical University, Tianjin 300211, China.

School of Laboratory Medicine, Tianjin Medical University, Tianjin 300203, China.

出版信息

Exp Cell Res. 2018 Jan 1;362(1):11-16. doi: 10.1016/j.yexcr.2017.09.038. Epub 2017 Sep 28.

DOI:10.1016/j.yexcr.2017.09.038

PMID:28965866

Abstract

Macrophages view as double agents in tumor progression. Trafficking of macrophages to the proximity of tumors is mediated by colony-stimulating factor-1 (CSF-1), a growth factor. In this study, we investigated the role of complement1q-binding protein (C1QBP)/ atypical protein kinase C ζ (PKCζ) in CSF-1-induced macrophage migration. Disruption of C1QBP expression impaired chemotaxis and adhesion of macrophage. Phosphorylation of PKCζ is an essential component in macrophage chemotaxis signaling pathway. C1QBP could interact with PKCζ in macrophage. C1QBP knockdown inhibited CSF-1 induced phosphorylation of PKCζ and integrin-β1. However, C1QBP knockdown didn't affect the phosphorylation of PKCζ induced by MCP-1. Furthermore, CSF-1 from RCC cell condition medium promoted macrophage chemotaxis and adhesion. Taken together, our results demonstrated that C1QBP plays an essential role in CSF-1 induced migration of macrophages.

摘要

巨噬细胞在肿瘤进展中被视为双重作用的细胞。巨噬细胞向肿瘤附近迁移是由集落刺激因子-1（CSF-1）介导的，CSF-1 是一种生长因子。在这项研究中，我们研究了补体 1q 结合蛋白（C1QBP）/非典型蛋白激酶 C ζ（PKCζ）在 CSF-1 诱导的巨噬细胞迁移中的作用。破坏 C1QBP 的表达会损害巨噬细胞的趋化性和黏附能力。PKCζ 的磷酸化是巨噬细胞趋化信号通路的一个重要组成部分。C1QBP 可以在巨噬细胞中与 PKCζ 相互作用。C1QBP 敲低抑制了 CSF-1 诱导的 PKCζ 和整合素-β1 的磷酸化。然而，C1QBP 敲低并不影响 MCP-1 诱导的 PKCζ 的磷酸化。此外，RCC 细胞条件培养基中的 CSF-1 促进了巨噬细胞的趋化性和黏附。总之，我们的结果表明 C1QBP 在 CSF-1 诱导的巨噬细胞迁移中发挥了重要作用。