Mechanistic Insight into BRMS1 Suppression of Metastasis

University Of Alabama At Birmingham, Birmingham AL

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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. [unreadable] [unreadable] [unreadable]