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CTBP‐BRCA1 modulates Epithelial Cell Fate in Breast Cancer
Author(s) -
byun Jung,
Gardner Kevin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.926.5
Subject(s) - microbiology and biotechnology , epithelial–mesenchymal transition , epigenetics , biology , chromatin , cell fate determination , cellular differentiation , histone , cancer research , metastasis , cancer , transcription factor , gene , genetics
Epithelial cells retain incredible plasticity. They can differentiate and self‐renew during embryonic development. The epithelial cells can lose their typical epithelial features and change to a mesenchymal state by activating epithelial mesenchymal transition (EMT), whose process is critical for breast cancer metastasis. BRCA1 is tumor suppressor gene that represses malignant transformation by safeguarding the fidelity of DNA replication chromosomal segregation and has been demonstrated to play a possible role in mammary differentiation. C‐terminal binding protein (CTBP) is a dimeric nuclear protein and an epigenetic regulator that is activated in the presence of NADH to recruit and target a variety of histone modifying complexes and transcriptional regulators to chromatin, thus providing a defined mechanism through which carbohydrate metabolism can drive epigenetic regulatory events. We have recently shown that CTBP drives epithelial mesenchymal transition (EMT), genome instability, and the acquisition of stem cell tumor‐initiating cell‐like pathways in breast cancer. Here we demonstrate that CTBP and BRCA1 competitively regulate epithelial features including epithelial polarity and lumen development in MCF10A 3D gland formation assays. Loss of BRCA1 appears to perturb mammary epithelial differentiation whereas CTBP depletion enhances epithelial differentiation. These findings define dynamic yet antagonist roles for CtBP and BRCA1 in mammary gland growth and development.