Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis

Cancer is characterized by cells that disobey the stringent control mechanisms of cellular processes such as division and growth, survival, homeostasis, motility, and tissue invasion. Signalling pathways, including the mitogen-activated protein kinase (MAPK) signalling pathways, regulate these cellular processes. Not unexpectedly, cancer cells display defects in signalling pathways due to mutations in genes encoding signal transduction proteins. The typical MAPK pathways transmit, amplify and translate signals through consecutive phosphorylation events engaging a MAPK kinase kinase, a MAPK kinase, and a MAPK, which finally phosphorylates substrates. These substrates can be non-protein kinases or protein kinases. The latter are referred to as MAPK-activating protein kinases. Escalating evidence exists that the MAPK signal transduction pathways can be implicated in metastasis. This review focuses on the specific roles of MAPK-activating protein kinases in metastasis and summarizes potential small inhibitors against MAPK-activating protein kinases that may find their way in cancer therapy.