SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/β-catenin signaling through stabilization of the WNT-receptor complex.

ABSTRACT: Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that SPARCL1 is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that SPARCL1 inhibits OS metastasis. We further demonstrated that SPARCL1-activated WNT/β-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT-receptor complex stabilization. Activation of WNT/β-catenin signaling contributes to the SPARCL1-mediated inhibitory effects on OS metastasis. Furthermore, we uncovered a paracrine effect of SPARCL1 on macrophage recruitment through activate

SUBMITTER: Zhao SJ 

PROVIDER: S-EPMC5851113 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature