Sorafenib controls the epithelialmesenchymal transition of ovarian cancer cells via EGF and the CD44HA signaling pathway in a cell typedependent manner.
Mol Med Rep
; 16(2): 1826-1836, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28627617
ABSTRACT
Cluster of differentiation (CD) 44 and epidermal growth factor (EGF) are closely involved in cellular migration and have been used as stem cell markers. Although the hyaluronan (HA)binding CD44 is responsible for enhanced cellular motility, the mechanism underlying its actions in various cell types and clinical conditions have yet to be elucidated. In the present study, the multikinase inhibitor sorafenib was used to investigate the diverse effects of EGF stimulation on epithelialmesenchymal transition (EMT) in ovarian cancer cells using immunoblotting and reverse transcriptionpolymerase chain reaction. In addition, the association between EGF and CD44/HA signaling pathways in the control of mesenchymal phenotype was determined by gene silencing with small interfering RNA transfection. EGF stimulation of ovarian cancer cells increased cellular migration, mesenchymal transition, CD44 expression and the activation of matrix metalloproteinase (MMP)2 and MMP9. Sorafenib effectively suppressed the loss of epithelial characteristics in EGFtreated SKOV3 ovarian cancer cells, via targeting the mitogenactivated protein kinase (MAPK)/extracellular signalregulated kinase (ERK) pathway. Although treatment of Caov3 ovarian cancer cells with sorafenib blocked the expression of mesenchymal phenotypes following EGF stimulation, EGFactivated Caov3 cells exhibited reduced MAPK/ERK signaling. Furthermore, EGFactivated Caov3 cells increased the expression of hyaluronan synthase 2 and HACD44 ligation in EGFexposed Caov3 cells, which resulted in the activation of the Ras/Raf/MEK signaling pathway, amplification of migratory activity and the expression of mesenchymal markers, including Ncadherin and vimentin. Furthermore, silencing EGFR in SKOV3 cells and CD44 in Caov3 cells suppressed their migratory activity, through inhibition of the MAPK/ERK pathway. The present results suggested that EGFmediated signaling may regulate metastasis and invasion of ovarian cancer cells, in a cancer cell typedependent manner.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Compostos de Fenilureia
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Transdução de Sinais
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Niacinamida
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Receptores de Hialuronatos
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Fator de Crescimento Epidérmico
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Transição Epitelial-Mesenquimal
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Ácido Hialurônico
Limite:
Female
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Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2017
Tipo de documento:
Article