Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance.
FEBS J
; 288(7): 2184-2202, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33090711
ABSTRACT
A growing body of evidence supports the notion that cancer resistance is driven by a small subset of cancer stem cells (CSC), responsible for tumor initiation, growth, and metastasis. Both CSC and chemoresistant cancer cells may share common qualities to activate a series of self-defense mechanisms against chemotherapeutic drugs. Here, we aimed to identify proteins in chemoresistant triple-negative breast cancer (TNBC) cells and corresponding CSC-like spheroid cells that may contribute to their resistance. We have identified several candidate proteins representing the subfamilies of DNA damage response (DDR) system, the ATP-binding cassette, and the 26S proteasome degradation machinery. We have also demonstrated that both cell types exhibit enhanced DDR when compared to corresponding parental counterparts, and identified RAD50 as one of the major contributors in the resistance phenotype. Finally, we have provided evidence that depleting or blocking RAD50 within the Mre11-Rad50-NBS1 (MRN) complex resensitizes CSC and chemoresistant TNBC cells to chemotherapeutic drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Hidrolases Anidrido Ácido
/
Proteínas de Ciclo Celular
/
Resistencia a Medicamentos Antineoplásicos
/
Proteínas de Ligação a DNA
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Neoplasias de Mama Triplo Negativas
/
Proteína Homóloga a MRE11
Limite:
Female
/
Humans
Idioma:
En
Revista:
FEBS J
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Espanha