Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation.
Nat Commun
; 14(1): 238, 2023 01 16.
Article
en En
| MEDLINE
| ID: mdl-36646707
ABSTRACT
Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Mecanotransducción Celular
/
Proteína Homeótica Nanog
/
Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2023
Tipo del documento:
Article