Abstract 3127: Roles of ERKs-RSK2 signaling in human cancers

Abstract

Abstract RSK2 is a member of p90RSK superfamily consisted with RSK1-4 and MSK1-2, and has suggested involving in many cellular processes including cell proliferation, differentiation, transformation and cancer development. Accumulating data obtained by our 16-year researches strongly demonstrated that RSK2 is a key player in cell transformation and cancer metastasis. We found that ectopic expression of RSK2 induced anchorage-independent cell transformation. Notably, knockdown of RSK2 strongly suppressed constitutive active-Ras (CA-Ras)-induced foci-formation, EGF-induced cell transformation and cancer cell growth in anchorage-independent condition. The results obtained from human skin cancer tissue array demonstrated that total protein levels and RSK2 activity were higher in cancer tissues than that of normal tissues. Molecular targeting of RSK2 or ERK1 and 2 with natural compounds demonstrated that ERKs-RSK2 signaling pathway plays a key role in cell transformation and cancer development. Moreover, inhibition of ERKs-RSK2 signaling suppressed NF-κB activity in JB6Cl41 cells. The EGF-induced NF-κB activity was abrogated up-regulation of COX-2 mRNA expression and COX-2 protein levels by inhibition of ERKs-RSK2 signaling pathway. Interestingly, magnolin, a specific inhibitor of ERK1 and ERK2, suppressed ERK-mediated MMP-2 and NF-κB-mediated MMP-9 expression. In addition, we found that the protein expression of N-cadherin involved in metastasis was markedly attenuated by inhibition of ERKs-RSK2 signaling pathway. Notably, magnolin suppressed the migration and invasion of lung cancer cells in a dose-dependent manner. Taken together, these results demonstrated that targeting of ERKs-RSK2 signaling is beneficial for the chemoprevention, and anti-invasion and -migration in cancer metastasis. Key words: MAPK pathway, Transformation, Metastasis, Molecular targets Citation Format: Yong Yeon Cho. Roles of ERKs-RSK2 signaling in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3127. doi:10.1158/1538-7445.AM2017-3127