CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo.
J Clin Invest
; 130(5): 2435-2450, 2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-32250342
ABSTRACT
The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti-CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Moléculas de Adesão Celular
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Regulação Neoplásica da Expressão Gênica
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Regulação para Cima
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Sistema de Sinalização das MAP Quinases
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Antígenos de Neoplasias
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article