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 in vivo. This functional significance of MTDH-SND1 interaction is further supported by clinical analysis of human breast cancer samples.
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Liling
authors: L
authors: Wan
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Xin
authors: X
authors: Lu
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Salina
authors: S
authors: Yuan
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Yong
authors: Y
authors: Wei
authors: McArdle Laboratory, Department of Oncology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Feng
authors: F
authors: Guo
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Minhong
authors: M
authors: Shen
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Min
authors: M
authors: Yuan
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Rumela
authors: R
authors: Chakrabarti
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Yuling
authors: Y
authors: Hua
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Heath A
authors: HA
authors: Smith
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors: Mario Andres
authors: MA
authors: Blanco
authors: Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08903, USA.
authors: Marina
authors: M
authors: Chekmareva
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors: Hao
authors: H
authors: Wu
authors: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Roderick T
authors: RT
authors: Bronson
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors: Bruce G
authors: BG
authors: Haffty
authors: McArdle Laboratory, Department of Oncology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Yongna
authors: Y
authors: Xing
authors: 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.
authors: Yibin
authors: Y
authors: Kang
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002472:Cell Transformation, Viral; D004720:Endonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000472:pathogenicity; D017258:Medroxyprogesterone Acetate; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D016601:RNA-Binding Proteins; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; C483038:Mtdh protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D017258:Medroxyprogesterone Acetate; D004720:Endonucleases; C095221:SND1 protein, human; C490640:Snd1 protein, mouse