The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility.
Cancer Biol Ther
; 21(6): 533-540, 2020 06 02.
Article
em En
| MEDLINE
| ID: mdl-32175798
ABSTRACT
Recent studies revealed that the histone demethylase KDM2B regulates the epithelial markers E-Cadherin and ZO-1, the RhoA/B/C-small-GTPases and actin cytoskeleton organization, in DU-145 prostate- and HCT-116 colon-tumor cells. Here we addressed the role of KDM2B in the activation of Focal Adhesion Kinase (FAK)-signaling and its involvement in regulating tumor cell motility. We used RT-PCR for gene transcriptional analysis, Western blotting for the assessment of protein expression and activity and wound-healing assay for the study of cell migration. KDM2B overexpression or silencing controls the activity of FAK in DU-145 prostate- and HCT-116 colon-tumor cells without affecting gene transcription and protein expression of this kinase. Upon KDM2B overexpression in DU-145 cells, significantly enhanced migration was observed, which was abolished in cells pretreated by the specific phosphoinositide-3 kinase (PI3 K) inhibitor LY294002, implying involvement of FAK/PI3 K signaling in the migration process. In line with this, the p85-PI3 K-subunit was downregulated upon knockdown of KDM2B in DU-145 cells, while the opposite effect became evident in KDM2B-overexpressing cells. These results revealed a novel functional role of KDM2B in regulating the activation of the FAK/PI3 K signaling in prostate cancer cells that participates in the control of cell motility.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Regulação Neoplásica da Expressão Gênica
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Movimento Celular
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Neoplasias do Colo
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Fosfatidilinositol 3-Quinases
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Proteínas F-Box
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Quinase 2 de Adesão Focal
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Histona Desmetilases com o Domínio Jumonji
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article