Breast Cancer Metastasis Suppressor 1 (BRMS1) is a metastasis suppressor gene discovered in 2000 and was found to suppress metastasis without blocking tumorigenicity in cell lines of human breast carcinoma, human melanoma, and murine carcinoma. Thus far, no definitive mechanism of action has been identified for this protein although it was recently discovered to interact with large protein complexes including histone deacetylases (HDACs). I hypothesize that BRMS1 mechanism of metastasis suppression is through interactions with a chromatin remodeling complex, mSin: HDAC. The first Specific Aim will define the proteins associated with this complex and identify those proteins directly interacting with BRMS1. The second Specific Aim will map the regions of BRMS1 that are important for critical protein interactions. Lastly, metastasis suppression will be quantified with selected mutants that have abolished protein associations. The results from these experiments will determine the regions of BRMS1 responsible for metastasis suppression and they will also identify the critical interactions involved in metastasis suppression. Understanding this complex """"""""pathway"""""""" may lead to novel strategies for treatment of this deadly disease. ? ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F09 (20))
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Jakowlew, Sonia B
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University of Alabama Birmingham
Schools of Medicine
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Lee, Seakwoo; Terry, Doris; Hurst, Douglas R et al. (2011) Protein Signatures in Human MDA-MB-231 Breast Cancer Cells Indicating a More Invasive Phenotype Following Knockdown of Human Endometase/Matrilysin-2 by siRNA. J Cancer 2:165-76
Hurst, Douglas R; Edmonds, Mick D; Scott, Gary K et al. (2009) Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 69:1279-83
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Richert, Monica M; Vaidya, Kedar S; Mills, Caroline N et al. (2009) Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone. Oncol Rep 21:761-7
Edmonds, Mick D; Hurst, Douglas R; Welch, Danny R (2009) Linking metastasis suppression with metastamiR regulation. Cell Cycle 8:2673-5
Hurst, Douglas R; Xie, Yi; Edmonds, Mick D et al. (2009) Multiple forms of BRMS1 are differentially expressed in the MCF10 isogenic breast cancer progression model. Clin Exp Metastasis 26:89-96
Phadke, Pushkar A; Vaidya, Kedar S; Nash, Kevin T et al. (2008) BRMS1 suppresses breast cancer experimental metastasis to multiple organs by inhibiting several steps of the metastatic process. Am J Pathol 172:809-17
Hurst, Douglas R; Xie, Yi; Vaidya, Kedar S et al. (2008) Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells. J Biol Chem 283:7438-44

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