LRP6 Ectodomain Prevents SDF-1/CXCR4-Induced Breast Cancer Metastasis to Lung.
Clin Cancer Res
; 25(15): 4832-4845, 2019 08 01.
Article
em En
| MEDLINE
| ID: mdl-31010839
ABSTRACT
PURPOSE:
Lung metastasis is an important cause of breast cancer-related deaths, in which SDF-1/CXCR4 signaling pathway plays a critical role. Single transmembrane protein LRP6 is viewed as an oncogene via activating the Wnt/ß-catenin signaling pathway. Our work aims to investigate the relationship between SDF-1/CXCR4 and LRP6 in breast cancer lung metastasis. EXPERIMENTALDESIGN:
We examined the expressions and functions of SDF-1/CXCR4 and LRP6 as well as their relationship in breast cancer in vitro and in vivo.RESULTS:
LRP6 ectodomain (LRP6N) directly bound to CXCR4 and competitively prevented SDF-1 binding to CXCR4. LRP6N prevented SDF-1/CXCR4-induced metastasis to lung and prolonged survival in mice bearing breast tumors, whereas LRP6 knockdown activated SDF-1/CXCR4 signal transduction and promoted lung metastasis and tumor death. Furthermore, patients with breast cancer with high CXCR4 expression had poor prognosis, which was exacerbated by low LRP6 expression but improved by high LRP6 expression. Interestingly, a secreted LRP6N was found in the serum of mice and humans, which was downregulated by the onset of cancer metastasis in both mice bearing breast cancer as well as in patients with breast cancer.CONCLUSIONS:
LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis. LRP6N also provides an interesting link between Wnt signaling and SDF-1/CXCR4 signaling, the two key pathways involved in cancer development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Biomarcadores Tumorais
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Receptores CXCR4
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Quimiocina CXCL12
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Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
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Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Screening_studies
Limite:
Adolescent
/
Adult
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Aged
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China