Abstract
Abstract Glioblastoma (GBM) is associated with high mortality in patients due in large part to the highly migratory and invasive nature of glioma cells. The 90kDa ribosomal S6 Kinases (RSKs) are a family of serine/theronine kinases that are an integral component of the extracellular signal regulated kinase (ERK)/ mitogen activated protein kinase (MAPK) pathway, which is highly active in many types of cancer. The RSK family contains four human isoforms (RSK1-4) that regulate a variety of cellular processes including cell proliferation, survival, and motility, however a role for individual RSK isoforms in GBM cell invasion has not clearly been defined. Here, we analyze the roles of RSK1-4 in glioblastoma cell invasion. Using transwell assays and a novel three-dimensional tumor spheroid assay, we found that the highly specific RSK inhibitor, BI-D1870, decreases glioblastoma cell motility and invasion. To identify which RSK isoform was associated with this decrease in invasion, we knocked down each RSK isoform using lentiviral mediated shRNA transduction and found that different RSK isoforms could decrease invasion depending on the cell line, without significantly affecting proliferation. Additionally, RSK2 knockdown in primary patient-derived glioblastoma cells decreased cell migration, and Kaplan-Meier analysis revealed that patients overexpressing RSK2 had a poorer prognosis compared to those expressing normal levels of RSK2. Our studies support a differential role for individual RSKs in glioblastoma invasion, suggesting that targeting RSKs may provide an effective means for the treatment of glioblastoma. Citation Format: Amanda Prechtl, Florian Sulzmaier, Pengfei Jiang, Santosh Kesari, Joe Ramos. RSK isoform regulation of migration and invasion in glioblastoma. [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 5007. doi:10.1158/1538-7445.AM2014-5007
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