Abstract
The 90 kDa ribosomal S6 kinase (RSK) family is a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. Deregulated RSK expression or activity has been associated with several human diseases, including cancer. RSK lies downstream of the Ras/mitogen-activated protein kinase (MAPK) signalling pathway and is directly phosphorylated by the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Significant advances in the field of RSK signalling have occurred in the past few years, unravelling novel RSK cellular substrates and biological functions as well as new RSK regulatory mechanisms. Together, these findings suggest that RSK may be a promising therapeutic target for the treatment of cancer, particularly those characterized by oncogenic mutations in components of the Ras signalling pathway. This article briefly describes our current knowledge on the impact of RSK on cell growth and proliferation, as well as RSK-dependent mechanisms associated with tumourigenesis. The potential of targeting RSK in cancer is discussed in light of available data on the biological functions of each RSK family members. Targeting RSK with small molecule inhibitors appears to be a promising path for cancer therapy, but several considerations need to be evaluated and will be discussed in detail.
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