Abstract 2686: RSK2/CREB/Fascin-1 signaling is important for tumor metastasis.

Abstract

Abstract Metastasis is the leading cause of death in patients with breast, lung or head and neck cancers. However, the molecular mechanisms underlying metastases in these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)-cAMP response element-binding (CREB) pathway is commonly activated in diverse metastatic human cancer cells, leading to upregulation of a CREB transcription target Fascin-1. We also observed that the protein expression patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples from HNSCC patients. Moreover, knockdown of RSK2 disrupts filopodia formation and bundling in highly invasive cancer cells, leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo, while expression of Fascin-1 significantly rescues these phenotypes. Furthermore, targeting RSK2 by a small molecule RSK inhibitor FMK-MEA effectively attenuated the invasive and metastatic potential of cancer cells in vitro and in vivo, respectively. Together, our findings for the first time link the RSK2-CREB signaling to filopodia formation and bundling by upregulating Fascin-1, providing a pro-invasive and pro-metastatic advantage to human cancers; protein effectors of RSK2-CREB-Fascin-1 pathway represents promising biomarkers and therapeutic targets in clinical prognosis and treatment of metastatic human cancers. Citation Format: Dan Li, Lingtao Jin, Gina Alesi, Young Mee Kim, Dongsheng Wang, Benjamin H Lee, Jack Taunton, Kelly R Magliocca, Zhuo Georgia Chen, Sumin Kang. RSK2/CREB/Fascin-1 signaling is important for tumor metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2686. doi:10.1158/1538-7445.AM2013-2686