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


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.

SUBMITTER: Wan L 

PROVIDER: S-EPMC4101059 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Wan Liling L   Lu Xin X   Yuan Salina S   Wei Yong Y   Guo Feng F   Shen Minhong M   Yuan Min M   Chakrabarti Rumela R   Hua Yuling Y   Smith Heath A HA   Blanco Mario Andres MA   Chekmareva Marina M   Wu Hao H   Bronson Roderick T RT   Haffty Bruce G BG   Xing Yongna Y   Kang Yibin Y  

Cancer cell 20140626 1


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 support  ...[more]

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