Abstract
Abstract Breast cancer is the most common cancer among women worldwide. BRMS1 is a metastasis suppressor that suppresses metastasis without significantly affecting the growth of a primary tumor. BRMS1 contains two coiled-coil motifs important for protein-protein interactions and two putative nuclear localization sequences (NLS - aa198-205 (NLS1) and aa239-245 (NLS2)) and one nuclear export signal which appear to mediate nuclear-cytoplasmic shuttling. Although NLS2 is not necessary for active transport into the nucleus, it is required for metastasis suppression (PMC3563580). A serine immediately upstream of NLS2 (S237) can be phosphorylated by cdk2 (PMC3037622). Therefore, we hypothesized that NLS2 and adjacent amino acids are critical mediators of metastasis suppression. To test this hypothesis, NLS2 (aa231-248) epitope-tagged with HA and GST was transduced into metastatic MDA-MB-231 and -435 breast carcinoma cells expressing green fluorescent protein and stable colonies were selected. BRMS1S237A-expressing MDA-MB-231 cells were no longer metastasis suppressed, suggesting a critical role for phosphorylation of BRMS1 in its metastasis suppressor activity. Studies are underway with full-length BRMS1S237D (phosphomimetic) as well as expression with truncated wild-type NLS2 and mutant (NLS2wt/S237A/S237D) to test whether the BRMS1 phosphorylation or the NLS2 domain itself is critical for metastasis suppressor activity. Support: CA87728, CA134981, P30-CA168524, Natl Fndn Cancer Res, Komen SAC11037, KS Bioscience Auth, NHMRC Citation Format: Lellys M. Contreras, Boris Sarcevic, Keke M. Pounds, Danny R. Welch. Breast Metastasis Suppressor 1 (BRMS1) phosphorylation appears necessary for metastasis suppressor activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3258. doi:10.1158/1538-7445.AM2015-3258
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