The PDGFRß/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer.
BMC Cancer
; 18(1): 586, 2018 May 23.
Article
en En
| MEDLINE
| ID: mdl-29792166
ABSTRACT
BACKGROUND:
CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels.METHODS:
The expression of CDCP1, PDGFRß and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRß was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFRß in TNBC clinical samples.RESULTS:
We discovered that PDGF-BB-mediated activation of PDGFRß increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock-down of PDGFRß in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFRß immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFRß axis in the modulation of CDCP1 expression.CONCLUSION:
We have identified PDGF-BB/PDGFRß-mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFRß and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Antígenos CD
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Moléculas de Adhesión Celular
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Regulación Neoplásica de la Expresión Génica
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Sistema de Señalización de MAP Quinasas
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Neoplasias de la Mama Triple Negativas
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Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Middle aged
Idioma:
En
Revista:
BMC Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia