Genomic regulation of invasion by STAT3 in triple negative breast cancer

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 epiderm...

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Bibliographic Details
Published in:	Oncotarget Vol. 8; no. 5; pp. 8226 - 8238
Main Authors:	McDaniel, Joy M, Varley, Katherine E, Gertz, Jason, Savic, Daniel S, Roberts, Brian S, Bailey, Sarah K, Shevde, Lalita A, Ramaker, Ryne C, Lasseigne, Brittany N, Kirby, Marie K, Newberry, Kimberly M, Partridge, E Christopher, Jones, Angela L, Boone, Braden, Levy, Shawn E, Oliver, Patsy G, Sexton, Katherine C, Grizzle, William E, Forero, Andres, Buchsbaum, Donald J, Cooper, Sara J, Myers, Richard M
Format:	Journal Article
Language:	English
Published:	United States Impact Journals LLC 31-01-2017
Subjects:	Cell Line, Tumor Cell Movement Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genome, Human Humans Neoplasm Invasiveness Neoplasm Metastasis Protein Binding Research Paper RNA Interference Signal Transduction STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Transcriptome Transfection Triple Negative Breast Neoplasms - genetics Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology ChIP-seq RNA-seq invasion TNBC STAT3
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1949-2553 1949-2553
DOI:	10.18632/oncotarget.14153