Abstract 4201: Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma

S100B is an effective and extensively used prognostic marker for melanoma, with increasing serum levels of S100B being predictive of disease stage, increased recurrence, and low overall patient survival. We have recently identified a mechanism by which S100B alters ERK-RSK signaling to facilitate the progression of melanoma. Elucidation of this novel mechanism will aid the development of new pharmacological drugs to inhibit tumor progression. We have identified and characterized several ERK-RSK downstream targets regulated by S100B expression. These data are consistent with a mechanism in which elevated S100B binds directly to RSK in a calcium-dependent manner to prevent ERK-mediated phosphorylation of RSK. Our structural studies have further elucidated the S100B-RSK interaction as a novel drug target in melanoma cells and we are currently screening compounds for inhibitors of the S100B-RSK interaction. Citation Format: Adam D. Pierce. Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4201. doi:10.1158/1538-7445.AM2014-4201