| http://purl.uniprot.org/citations/34847079 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34847079 | http://www.w3.org/2000/01/rdf-schema#comment | "Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate premetastatic niche and bone tropism are largely unknown. In this study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating the WNT inhibitor DKK1 through Gαq and β-catenin signaling. DKK1 directly facilitated OP recruitment through suppression of its receptor LDL receptor-related protein 5 (LRP5) but not LRP6, upregulating Rnasek expression via inhibition of canonical WNT signaling. In clinical samples, RSPO2, LGR4, and DKK1 expression showed a positive correlation with BCa bone metastasis. Furthermore, soluble LGR4 extracellular domain (ECD) protein, acting as a decoy receptor for RSPO2 and RANKL, significantly alleviated bone metastasis and osteolytic lesions in a mouse bone metastasis model. These findings provide unique insights into the functional role of OPs as key components of the premetastatic niche for BCa bone metastasis and identify RSPO2/RANKL-LGR4 signaling as a promising target for inhibiting BCa bone metastasis."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci144579"xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Chen G."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Ding Y."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Gao Y."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Jiang W."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Hu G."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Gao J."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Liu M."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Luo J."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Li R."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Zhang X.H."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Yang Z."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Xu Z."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Xiao J."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Yuan Z."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Wang N."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Xue X."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "He L."xsd:string |
| http://purl.uniprot.org/citations/34847079 | http://purl.uniprot.org/core/author | "Yue F."xsd:string |