The Transient Receptor Potential Melastatin 7 Channel Regulates Pancreatic Cancer Cell Invasion through the Hsp90α/uPA/MMP2 pathway.
Neoplasia
; 19(4): 288-300, 2017 04.
Article
em En
| MEDLINE
| ID: mdl-28284058
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis. There is an urgent need to better understand the molecular mechanisms that regulate PDAC cell aggressiveness. The transient receptor potential melastatin 7 (TRPM7) is a nonselective cationic channel that mainly conducts Ca2+ and Mg2+. TRPM7 is overexpressed in numerous malignancies including PDAC. In the present study, we used the PANC-1 and MIA PaCa-2 cell lines to specifically assess the role of TRPM7 in cell invasion and matrix metalloproteinase secretion. We show that TRPM7 regulates Mg2+ homeostasis and constitutive cation entry in both PDAC cell lines. Moreover, cell invasion is strongly reduced by TRPM7 silencing without affecting the cell viability. Conditioned media were further studied, by gel zymography, to detect matrix metalloproteinase (MMP) secretion in PDAC cells. Our results show that MMP-2, urokinase plasminogen activator (uPA), and heat-shock protein 90α (Hsp90α) secretions are significantly decreased in TRPM7-deficient PDAC cells. Moreover, TRPM7 expression in human PDAC lymph node metastasis is correlated to the channel expression in primary tumor. Taken together, our results show that TRPM7 is involved in PDAC cell invasion through regulation of Hsp90α/uPA/MMP-2 proteolytic axis, confirming that this channel could be a promising biomarker and possibly a target for PDAC metastasis therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Ativador de Plasminogênio Tipo Uroquinase
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Transdução de Sinais
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Proteínas Serina-Treonina Quinases
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Proteínas de Choque Térmico HSP90
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Metaloproteinase 2 da Matriz
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Canais de Cátion TRPM
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Neoplasia
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article