Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells.
PLoS One
; 15(10): e0241423, 2020.
Article
em En
| MEDLINE
| ID: mdl-33119681
ABSTRACT
Mesenchymal stem cells (MSCs) are recruited and activated by solid tumors and play a role in tumor progression and metastasis. Here we show that MSCs promote metastasis in a panel of non-small cell lung cancer (NSCLC) cells. MSCs elicit transcriptional alterations in lung cancer cells leading to increased expression of factors implicated in the epithelial-to-mesenchymal transition (EMT) and secreted proteins including matrix metalloproteinase-9 (MMP9). MSCs enhance secretion of enzymatically active MMP9 in a panel of lung adenocarcinoma cells. High expression of MMP9 is linked to low survival rates in lung adenocarcinoma patients. Notably, we found that ABL tyrosine kinases are activated in MSC-primed lung cancer cells and functional ABL kinases are required for MSC-induced MMP9 expression, secretion and proteolytic activity. Importantly, ABL kinases are required for MSC-induced NSCLC metastasis. These data reveal an actionable target for inhibiting MSC-induced metastatic activity of lung adenocarcinoma cells through disruption of an ABL kinase-MMP9 signaling axis activated in MSC-primed lung cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas Proto-Oncogênicas c-abl
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Carcinoma Pulmonar de Células não Pequenas
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Metaloproteinase 9 da Matriz
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Células-Tronco Mesenquimais
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Neoplasias Pulmonares
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article