Defining the role of the RSK isoforms in cancer

Abstract The 90 kDa ribosomal S6 kinase (RSK) family is a group of Ser/Thr protein kinases (RSK1-4) that function downstream of the Ras/mitogen-activated protein kinase (MAPK) signalling pathway. RSK regulates many substrates involved in cell survival, growth, and proliferation, and as such, deregulated RSK activity has been associated with multiple cancer types. RSK expression and activity are dysregulated in several malignancies, including breast, prostate, and lung cancer, and available evidence suggests that RSK may be a promising cancer therapeutic target. Current limitations include the lack of RSK inhibitors with suitable pharmacokinetics and selectivity toward particular isoforms. This review briefly describes the current knowledge on RSK activation and function, with a particular emphasis on RSK-dependent mechanisms associated with tumorigenesis and pharmacological inhibition.