Dual-specificity MAP kinase (MAPK) phosphatases (MKPs) and their involvement in cancer

Mitogen-activated protein kinase (MAPK) cascades regulate diverse cellular functions including proliferation, differentiation, migration and apoptosis. The abnormal regulation or activity of MAPK signalling pathways has been implicated as a key event in the initiation and progression of many human cancers. Furthermore, MAPK signalling also plays a key role in the cellular response to many cancer treatments, including radiation and chemotherapeutic drugs. Dual-specificity mitogen-activated protein kinase phosphatases (DUSPs or MKPs) dephosphorylate the key threonine and tyrosine residues within the activation loop of the MAPKs and act as negative regulators to modulate the spatiotemporal dynamics of MAPK activity and thus the biological outcome of signalling. There is accumulating evidence that alterations in the expression and activities of MKPs are found in a wide range of cancers. However, this data is complex and often contradictory with evidence for both oncogenic and tumour suppressive roles, depending on disease and cellular context. This review summarises our current understanding of the role(s) that these enzymes might play in the oncogenic process and suggests avenues for further studies. Such work will lead to novel insights into the abnormal regulation of MAPK activity in cancer and reveal novel therapeutic approaches.