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Oncotarget. 2017 Jan 31;8(5):8226-8238. doi: 10.18632/oncotarget.14153.

Genomic regulation of invasion by STAT3 in triple negative breast cancer.

Author information

1
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
2
The University of Alabama in Huntsville, Huntsville, AL 35899, USA.
3
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
4
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
5
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA.
6
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
7
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.

Abstract

Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as "triple negative breast cancer" (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 5 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.

KEYWORDS:

ChIP-seq; RNA-seq; STAT3; TNBC; invasion

PMID:
28030809
PMCID:
PMC5352396
DOI:
10.18632/oncotarget.14153
[Indexed for MEDLINE]
Free PMC Article

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