RhBMP-2 Activates Hippo Signaling through RASSF1 in Esophageal Cancer Cells.
Sci Rep
; 6: 26821, 2016 05 27.
Article
em En
| MEDLINE
| ID: mdl-27230238
ABSTRACT
Despite that recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported as a stimulatory effecter of cancer cell growth because of its characteristic like morphogen, the biological functions of rhBMP-2 in human esophageal cancer cells are unknown. The purpose of this study was to investigate whether rhBMP-2 has an inhibitory effect on the growth of human esophageal squamous carcinoma cells (ESCC). RhBMP-2 significantly inhibited proliferation of ESCC cells in a dose-dependent manner in the MTT assay. Cell cycle arrest at the G1 phase was induced 24 h after rhBMP2 treatment. RhBMP-2 also reduced cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and stimulated p-Smad1/5/8, p53, and p21 levels at 12 h. In contrast, rhBMP-2 diminished poly (ADP-ribose) polymerase (PARP) protein expression levels and activated cleaved PARP, cleaved caspase-7, and cleaved-caspase 9 levels in ESCC cells. In addition, rhBMP-2 increased MST1, MOB1, and p-YAP protein levels and the RASSF1 binds Mst1 more upon treatment with rhBMP2. The induced p-YAP expression in TE-8 and TE-12 cells by rhBMP-2 was reversed by the RASSF1 knockdown. In vivo study, rhBMP-2 decreased tumor volume following subcutaneous implantation and showed higher radiologic score (less bony destruction) after femoral implantation compared to those in a control group. These results suggest that rhBMP-2 inhibits rather than activates proliferation of human esophageal cancer cells which is mediated through activating the hippo signaling pathway.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
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Carcinoma de Células Escamosas
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Fator de Crescimento Transformador beta
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Proteínas Serina-Treonina Quinases
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Proteínas Supressoras de Tumor
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Proteína Morfogenética Óssea 2
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Pontos de Checagem da Fase G1 do Ciclo Celular
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article