Transcriptional network analysis identifies BACH1 as a master regulator of breast cancer bone metastasis

Yajun Liang, Heng Wu, Rong Lei, Robert A. Chong, Yong Wei, Xin Lu, Ilias Tagkopoulos, Sun Yuan Kung, Qifeng Yang, Guohong Hu, Yibin Kang

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


The application of functional genomic analysis of breast cancer metastasis has led to the identification of a growing number of organ-specific metastasis genes, which often function in concert to facilitate different steps of the metastatic cascade. However, the gene regulatory network that controls the expression of these metastasis genes remains largely unknown. Here, we demonstrate a computational approach for the deconvolution of transcriptional networks to discover master regulators of breast cancer bone metastasis. Several known regulators of breast cancer bone metastasis such as Smad4 and HIF1 were identified in our analysis. Experimental validation of the networks revealed BACH1, a basic leucine zipper transcription factor, as the common regulator of several functional metastasis genes, including MMP1 and CXCR4. Ectopic expression of BACH1 enhanced the malignance of breast cancer cells, and conversely, BACH1 knockdown significantly reduced bone metastasis. The expression of BACH1 and its target genes was linked to the higher risk of breast cancer recurrence in patients. This study established BACH1 as the master regulator of breast cancer bone metastasis and provided a paradigm to identify molecular determinants in complex pathological processes.

Original languageEnglish (US)
Pages (from-to)33533-33544
Number of pages12
JournalJournal of Biological Chemistry
Issue number40
StatePublished - Sep 28 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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