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

Cancer cell 2014 Jul 14

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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. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Liling Wan, Xin Lu, Salina Yuan, Yong Wei, Feng Guo, Minhong Shen, Min Yuan, Rumela Chakrabarti, Yuling Hua, Heath A Smith, Mario Andres Blanco, Marina Chekmareva, Hao Wu, Roderick T Bronson, Bruce G Haffty, Yongna Xing, Yibin Kang. MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors. Cancer cell. 2014 Jul 14;26(1):92-105