ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance.
Cell
; 184(20): 5215-5229.e17, 2021 09 30.
Article
em En
| MEDLINE
| ID: mdl-34559986
ABSTRACT
Estrogen receptor α (ERα) is a hormone receptor and key driver for over 70% of breast cancers that has been studied for decades as a transcription factor. Unexpectedly, we discover that ERα is a potent non-canonical RNA-binding protein. We show that ERα RNA binding function is uncoupled from its activity to bind DNA and critical for breast cancer progression. Employing genome-wide cross-linking immunoprecipitation (CLIP) sequencing and a functional CRISPRi screen, we find that ERα-associated mRNAs sustain cancer cell fitness and elicit cellular responses to stress. Mechanistically, ERα controls different steps of RNA metabolism. In particular, we demonstrate that ERα RNA binding mediates alternative splicing of XBP1 and translation of the eIF4G2 and MCL1 mRNAs, which facilitates survival upon stress conditions and sustains tamoxifen resistance of cancer cells. ERα is therefore a multifaceted RNA-binding protein, and this activity transforms our knowledge of post-transcriptional regulation underlying cancer development and drug response.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Proteínas de Ligação a RNA
/
Resistencia a Medicamentos Antineoplásicos
/
Receptor alfa de Estrogênio
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China