Cancer cell, 2014-07, Vol.26 (1), p.92-105
2014
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- Autor(en) / Beteiligte
- Titel
- MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors
- Ist Teil von
- Cancer cell, 2014-07, Vol.26 (1), p.92-105
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- ScienceDirect
- Beschreibungen/Notizen
- 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. [Display omitted] •MTDH deficiency inhibits diverse oncogene- or carcinogen-induced tumorigenesis•MTDH is selectively required for TICs but not normal mammary stem cells•MTDH-mediated stabilization of SND1 confers survival advantage under stress•MTDH interaction is required for SND1-dependent expression of prosurvival genes Wan et al. show that metadherin (MTDH) is important for mammary tumor-initiating cells (TIC), but not for mammary stem cells. MTDH interacts with SND1 to support mammary epithelial cell survival under oncogenic/stress conditions; interfering with this interaction reduces TIC tumorigenenic potential.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108eISSN: 1878-3686DOI: 10.1016/j.ccr.2014.04.027Titel-ID: cdi_proquest_miscellaneous_1635028032
- Format
- –
- Schlagworte
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Breast Neoplasms - chemically induced, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Breast Neoplasms - virology, Cell Adhesion Molecules - metabolism, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Cell Transformation, Neoplastic - pathology, Cell Transformation, Viral, Female, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, HEK293 Cells, Humans, Mammary Glands, Animal - metabolism, Mammary Glands, Animal - pathology, Mammary Glands, Animal - virology, Mammary Tumor Virus, Mouse - genetics, Mammary Tumor Virus, Mouse - pathogenicity, Medroxyprogesterone Acetate, Membrane Proteins - genetics, Membrane Proteins - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neoplasm Invasiveness, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Phenotype, Protein Binding, RNA Interference, Time Factors, Transfection, Tumor Cells, Cultured