An integrated systems biology approach identifies TRIM25 as a key determinant of breast cancer metastasis Journal Article

Authors: Walsh, L. A.; Alvarez, M. J.; Sabio, E. Y.; Reyngold, M.; Makarov, V.; Mukherjee, S.; Lee, K. W.; Desrichard, A.; Turcan, Ş; Dalin, M. G.; Rajasekhar, V. K.; Chen, S.; Vahdat, L. T.; Califano, A.; Chan, T. A.
Article Title: An integrated systems biology approach identifies TRIM25 as a key determinant of breast cancer metastasis
Abstract: At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. © 2017 The Authors
Keywords: metastasis; breast; transcription; cancer; aracne; efp; marina; trim25; viper
Journal Title: Cell Reports
Volume: 20
Issue: 7
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2017-08-15
Start Page: 1623
End Page: 1640
Language: English
DOI: 10.1016/j.celrep.2017.07.052
PROVIDER: scopus
PUBMED: 28813674
PMCID: PMC5985663
Notes: Article -- Export Date: 5 September 2017 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    222 Chan
  2. Marsha Laufer
    26 Laufer
  3. Sevin Turcan
    25 Turcan
  4. Logan Alexander Walsh
    19 Walsh
  5. Vladimir Makarov
    32 Makarov
  6. Ken-Wing   Lee
    5 Lee
  7. Martin Gustav Dalin
    4 Dalin
  8. Erich Sabio
    1 Sabio