Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway.
Oncotarget
; 7(49): 81423-81434, 2016 Dec 06.
Article
em En
| MEDLINE
| ID: mdl-27833078
ABSTRACT
Dapper homolog 1 alpha (DACT1α) is a member of DACT family and an important regulator in the planar cell polarity pathway. We aim to clarify its functional role in metastasis ability of gastric cancer. DACT1α was silenced in all gastric cancer cell lines (8/8), but expressed in normal gastric tissue. Ectopic expression of DACT1α in silenced gastric cancer cell lines (AGS, BGC823 and MGC803) by stable transfection significantly suppressed cancer cell spreading (P < 0.05), migration (P < 0.01) and invasion (P < 0.01). These effects were associated with downregulation of planar cell polarity pathway related genes involved in cell proliferation (PDGFB, VEGFA), adhesion (ITGA1, ITGA2, ITGA3, ITGB3) and migration/invasion (PLAU, MMP9, MCAM, Dvl-2 and JNK). DACT1α promoter methylation was detected in 205 gastric cancers and 20 normal controls by direct bisulfite genomic sequencing. DACT1α methylation was detected in 29.3% (60/205) of gastric cancer patients, but not in normal tissues. DACT1α methylation was associated with poor survival of gastric cancer patients. In conclusion, DACT1α plays a pivotal role as a potential tumor suppressor in migration and invasion of gastric cancer. DACT1α methylation may serve as a biomarker for the prognosis of gastric cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Proteínas Nucleares
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Movimento Celular
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Proteínas Supressoras de Tumor
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Proteínas Adaptadoras de Transdução de Sinal
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Plasticidade Celular
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article