Roles of PIM serine/threonine kinases in cancers

The Pim family of Ser/Thr kinases has been first identified in murine Moloney leukemia virus induced lymphomas, and is composed of three isoforms, Pim-1, Pim-2 and Pim-3. The following studies show that Pims are constitutively activated in many cancers. Of which, Pim-1 and Pim-2 are found to show the elevated levels mostly in hematologic malignancies and prostate cancer, while increased Pim-3 expression was mainly observed in different solid tumors.

     Several studies have demonstrated that Pim-1 is a major downstream target of the STATs induced by a large variety of receptors such as IL-2, IL-7, IL-9, IFNγ, EPO, and FLT3. On posttranscriptional level, Pim-1 kinase can protect from proteasomal degradation by heat shock proteins. About other two members, investigation indicated that lacking Pim-1 has led to compensatory activation of Pim-2, and Pim-3 also can substitute for Pim-1 and Pim-2 in lymphomagenesis.
     The oncogenic activity of Pim has reported to be mediated by multiple cellular factors. For example, some studies suggested that Pim kinases might participate in a complex feedback mechanism regulating the JAK2/STAT5 signaling pathway that plays an important role in induction and maintenance of hematologic malignancies[2]. In addition, p53 regulation for induction of malignant transformation may also considered to be mediated by Pim[2].
     At present, Pim has been found to proposed to be a prognostic marker in a variety of cancers, and over 50 potential Pim inhibitors have become public. However, very little about upstream regulators that functionally modify Pim is understood, thus further studies on the subject are still needed in order to know more about the regulation of Pim pathway.
References
[1]. J Clin Oncol. 2009;27(26):4422-32.
[2]. Haematologica 2010;95:1004-1015.

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