TOB1 suppresses proliferation in K-Ras wild-type pancreatic cancer.
Cancer Med
; 9(4): 1503-1514, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31891232
ABSTRACT
TOB1 participates in various kinds of cancers. However, its role in pancreatic cancer has rarely been reported. In this study, we explored the expression and mechanisms of TOB1 in regulating the malignant phenotype of pancreatic cancer cells. TOB1 expression was determined by data mining and immunohistochemistry (IHC), and its localization was observed by immunofluorescence. CCK-8 cell proliferation, colony formation, flow cytometric, transwell migration, and Western blot (WB) assays were used to examine how it impacts the malignant phenotype of pancreatic cancer. Furthermore, Foxa2 binding to TOB1 was tested by dual-luciferase reporter assays, and RNA-Seq was performed to identify signaling pathways. We found TOB1 was downregulated in pancreatic cancer tissues and was mainly located in the cytoplasm. TOB1 overexpression reduced the proliferation of K-Ras wild-type pancreatic cancer cells but made no difference to cell migration and invasion. Foxa2 overexpression significantly enhanced TOB1 promoter activity. Moreover, overexpressing TOB1 substantially enriched the calcium pathway in K-Ras wild-type pancreatic cancer cells. In conclusion, TOB1 may suppress the proliferation of K-Ras wild-type pancreatic cancer cells by regulating calcium pathway genes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Regulação Neoplásica da Expressão Gênica
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Proteínas Supressoras de Tumor
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Peptídeos e Proteínas de Sinalização Intracelular
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Fator 3-beta Nuclear de Hepatócito
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article