Identification of staphylococcal nuclease domain-containing 1 (SND1) as a metadherin-interacting protein with metastasis-promoting functions

Mario Andres Blanco, Maša Alečković, Yuling Hua, Tuo Li, Yong Wei, Zhen Xu, Ileana M. Cristea, Yibin Kang

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis.

Original languageEnglish (US)
Pages (from-to)19982-19992
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number22
DOIs
StatePublished - Jun 3 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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