@article{6553313a46fc4f4e9ce3088b8bb66602,
title = "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 invivo. This functional significance of MTDH-SND1 interaction is further supported by clinical analysis of human breast cancer samples.",
author = "Liling Wan and Xin Lu and Salina Yuan and Yong Wei and Feng Guo and Minhong Shen and Min Yuan and Rumela Chakrabarti and Yuling Hua and Smith, \{Heath A.\} and Blanco, \{Mario Andres\} and Marina Chekmareva and Hao Wu and Bronson, \{Roderick T.\} and Haffty, \{Bruce G.\} and Yongna Xing and Yibin Kang",
note = "Funding Information: We thank J.T. Eggenschwiler, J. Levorse, and M. Bhaumik for helping with the generation of Mtdh -knockout and MMTV-Mtdh transgenic mice, R.A. Weinberg for the HMLE-N cell line, A.L. Welm and M.T. Lewis for the human breast cancer PDX lines, K. Pantel and H. Wikman for providing human breast TMAs, W. Muller for the pMMTV-SV40 plasmid, X.H. Zhang for bioinformatic analysis, C. DeCoste for assistance with flow cytometry, and L. Cong, W. Chen for IHC analysis. The work was supported by a Charlotte Elizabeth Procter Fellowship to L.W. and grants from the Department of Defense (BC123187), Brewster Foundation, Komen for the Cure, and the NIH (R01CA134519) to Y.K. and a grant from Breast Cancer Research foundation to B.G.H. This research was also supported by the Transgenic/Knockout, Tissue Analytic Service and Flow Cytometry Shared Resources of the Cancer Institute of New Jersey (P30CA072720). ",
year = "2014",
month = jul,
day = "14",
doi = "10.1016/j.ccr.2014.04.027",
language = "English (US)",
volume = "26",
pages = "92--105",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}