MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors.
Cancer Cell
; 26(1): 92-105, 2014 Jul 14.
Article
in En
| MEDLINE
| ID: mdl-24981741
ABSTRACT
The Metadherin gene (MTDH) is prevalently amplified in breast cancer and associated with poor prognosis; however, its functional contribution to tumorigenesis is poorly understood. Using mouse models representing different subtypes of breast cancer, we demonstrated that MTDH plays a critical role in mammary tumorigenesis by regulating oncogene-induced expansion and activities of tumor-initiating cells (TICs), whereas it is largely dispensable for normal development. Mechanistically, MTDH supports the survival of mammary epithelial cells under oncogenic/stress conditions by interacting with and stabilizing Staphylococcal nuclease domain-containing 1 (SND1). Silencing MTDH or SND1 individually or disrupting their interaction compromises tumorigenenic potential of TICs in vivo. This functional significance of MTDH-SND1 interaction is further supported by clinical analysis of human breast cancer samples.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
/
Breast Neoplasms
/
Nuclear Proteins
/
Cell Adhesion Molecules
/
Cell Transformation, Neoplastic
/
Cell Proliferation
/
Mammary Glands, Animal
/
Membrane Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2014
Document type:
Article
Affiliation country:
Estados Unidos