MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors

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

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)92-105
Number of pages14
JournalCancer Cell
Volume26
Issue number1
DOIs
StatePublished - Jul 14 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors'. Together they form a unique fingerprint.

Cite this