SMARCE1 is required for the invasive progression of in situ cancers.
Proc Natl Acad Sci U S A
; 114(16): 4153-4158, 2017 04 18.
Article
em En
| MEDLINE
| ID: mdl-28377514
ABSTRACT
Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Proteínas Cromossômicas não Histona
/
Movimento Celular
/
Carcinoma Ductal de Mama
/
Carcinoma Intraductal não Infiltrante
/
Proteínas de Ligação a DNA
/
Recidiva Local de Neoplasia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article