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Cancer Cell. 2014 Jul 14;26(1):92-105. doi: 10.1016/j.ccr.2014.04.027. Epub 2014 Jun 26.

MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors.

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
2
McArdle Laboratory, Department of Oncology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53706, USA.
3
Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08903, USA.
4
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
5
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. Electronic address: ykang@princeton.edu.

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.

PMID:
24981741
PMCID:
PMC4101059
DOI:
10.1016/j.ccr.2014.04.027
[Indexed for MEDLINE]
Free PMC Article

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