Journal article
Aberrant BAF57 Signaling Facilitates Prometastatic Phenotypes
Clinical cancer research, v 19(10), pp 2657-2667
15 May 2013
PMID: 23493350
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose: BAF57, a component of the switching-defective and sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex conglomerate, modulates androgen receptor activity to promote prostate cancer. However, the molecular consequences of tumor-associated BAF57 expression have remained undefined in advanced disease such as castration-resistant prostate cancer and/or metastasis.
Experimental Design: Clinical human specimens of primary and metastatic prostate cancer were immunohistochemically examined for tumor-grade association of BAF57 expression. Global gene expression analyses were conducted in models mimicking tumor-associated BAF57 expression. Aberrant BAF57-dependent gene expression changes, bypass of androgen-mediated signaling, and chromatin-specific SWI/SNF complex alterations with respect to cytoskeletal remodelers such as integrins were validated. Cell migration assays were used to profile the biologic phenotypes conferred under conditions simulating tumor-derived BAF57 expression.
Results: Immunohistochemical quantitation of primary human specimens revealed that BAF57 was significantly and aberrantly elevated as a function of tumor grade. Critically, gene expression analyses showed that BAF57 deregulation circumvented androgen-mediated signaling, elicited alpha 2 integrin upregulation, and altered other SWI/SNF complex components at the alpha 2 integrin locus. BAF57-dependent alpha 2 integrin induction conferred a prometastatic migratory advantage, which was attenuated by anti-alpha 2 integrin antibody blockade. Furthermore, BAF57 was found to be markedly upregulated in human prostate cancer metastases of the lung, lymph node, and dura.
Conclusion: The findings herein, identifying tumor-associated BAF57 perturbation as a means to bypass androgen- signaling events that facilitate novel prometastatic phenotypes, link BAF57 upregulation to tumor dissemination. These data thereby establish BAF57 as a putative marker of metastatic potential that could be leveraged for therapeutic intervention. (C) 2013 AACR.
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Details
- Title
- Aberrant BAF57 Signaling Facilitates Prometastatic Phenotypes
- Creators
- Sucharitha Balasubramaniam - Thomas Jefferson UniversityClay E. S. Comstock - University of Southern CaliforniaAdam Ertel - University of Southern CaliforniaKwang Won Jeong - University of Southern CaliforniaMichael R. Stallcup - University of Southern CaliforniaSankar Addya - University of Southern CaliforniaPeter A. McCue - University of Southern CaliforniaWilliam F. Ostrander - University of Southern CaliforniaMichael A. Augello - University of Southern CaliforniaKaren E. Knudsen - University of Southern California
- Publication Details
- Clinical cancer research, v 19(10), pp 2657-2667
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 11
- Grant note
- PC094507 / Department of Defense; United States Department of Defense R01DK043093 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) CA159941; DK043093 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA116777 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000318911600010
- Scopus ID
- 2-s2.0-84878042268
- Other Identifier
- 991019176640404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology