Warfel Noel A, Kraft Andrew S
Department of Cellular and Molecular Medicine, Tucson, AZ 85724, United States; University of Arizona Cancer Center, Tucson, AZ 85724, United States.
Department of Medicine, Tucson, AZ 85724, United States; University of Arizona Cancer Center, Tucson, AZ 85724, United States.
Pharmacol Ther. 2015 Jul;151:41-9. doi: 10.1016/j.pharmthera.2015.03.001. Epub 2015 Mar 5.
The initiation and progression of human cancer is frequently linked to the uncontrolled activation of survival kinases. Two such pro-survival kinases that are commonly amplified in cancer are PIM and Akt. These oncogenic proteins are serine/threonine kinases that regulate tumorigenesis by phosphorylating substrates that control the cell cycle, cellular metabolism, proliferation, and survival. Growing evidence suggests that cross-talk exists between the PIM and Akt kinases, indicating that they control partially overlapping survival signaling pathways that are critical to the initiation, progression, and metastatic spread of many types of cancer. The PI3K/Akt signaling pathway is activated in many human tumors, and it is well established as a promising anticancer target. Likewise, based on the role of PIM kinases in normal and tumor tissues, it is clear that this family of kinases represents an interesting target for anticancer therapy. Pharmacological inhibition of PIM has the potential to significantly influence the efficacy of standard and targeted therapies. This review focuses on the regulation of PIM kinases, their role in tumorigenesis, and the biological impact of their interaction with the Akt signaling pathway on the efficacy of cancer therapy.
人类癌症的发生和发展常常与存活激酶的失控激活有关。在癌症中通常会扩增的两种此类促存活激酶是PIM和Akt。这些致癌蛋白是丝氨酸/苏氨酸激酶，它们通过磷酸化控制细胞周期、细胞代谢、增殖和存活的底物来调节肿瘤发生。越来越多的证据表明，PIM激酶和Akt激酶之间存在相互作用，这表明它们控制着部分重叠的存活信号通路，这些通路对多种类型癌症的发生、发展和转移扩散至关重要。PI3K/Akt信号通路在许多人类肿瘤中被激活，并且它已被确立为一个有前景的抗癌靶点。同样，基于PIM激酶在正常组织和肿瘤组织中的作用，很明显该激酶家族是抗癌治疗的一个有趣靶点。对PIM的药理学抑制有可能显著影响标准疗法和靶向疗法的疗效。本综述重点关注PIM激酶的调节、它们在肿瘤发生中的作用，以及它们与Akt信号通路的相互作用对癌症治疗疗效的生物学影响。
