CPSF6 is a Clinically Relevant Breast Cancer Vulnerability Target: Role of CPSF6 in Breast Cancer.
EBioMedicine
; 21: 65-78, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28673861
ABSTRACT
Breast cancer represents a major health challenge. The majority of breast cancer deaths are due to cancer progression/recurrence for which no efficient therapies exist. Aggressive breast cancers are characterized by loss of cellular differentiation. Defining molecular mechanisms/targets contributing to cancer aggressiveness is needed to guide the design of new screening and targeted treatments. Here, we describe a novel tumor promoting function for the Cleavage and Polyadenylation Factor-6 (CPSF6). Importantly, aggressive breast cancer cells of luminal B, HER2-overexpressing and triple negative subtypes show dependency on CPSF6 for viability and tumorigenic capacity. Mechanistically, we found CPSF6 to interact with components of the A-to-I RNA editing machinery, paraspeckles and ADAR1 enzyme, and to be required for their physical integrity. Clinically, we found CPSF6 and all core paraspeckles proteins to be overexpressed in human breast cancer cases and their expression to correlate with poor patient outcomes. Finally, we found prolactin, a key mammary differentiation factor, to suppress CPSF6/RNA editing activity. Together, this study revealed CPSF6 as a molecular target with clinical relevance for prognosis and therapy in breast cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Fatores de Poliadenilação e Clivagem de mRNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2017
Tipo de documento:
Article