PIM kinase (and Akt) biology and signaling in tumors.
PIM kinase (and Akt) biology and signaling in tumors.
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DOI：
10.1016/j.pharmthera.2015.03.001
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发表时间：
2015-07
影响因子：
13.5
通讯作者：
Kraft AS
中科院分区：
文献类型：
--
作者：
Warfel NA;Kraft AS
人类癌症的发生和发展通常与生存激酶的不受控制的激活有关。在癌症中通常扩增的两种这样的促存活激酶是PIM和Akt。这些致癌蛋白是丝氨酸/苏氨酸激酶，其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和Akt激酶之间存在串扰，表明它们控制部分重叠的生存信号通路，这些通路对许多类型癌症的起始、进展和转移扩散至关重要。PI 3 K/Akt信号通路在许多人类肿瘤中被激活，并且它被公认为是一种有前途的抗癌靶点。同样，基于PIM激酶在正常和肿瘤组织中的作用，很明显，该激酶家族代表了抗癌治疗的有趣靶点。PIM的药理学抑制有可能显著影响标准和靶向治疗的疗效。本文综述了PIM激酶的调节，它们在肿瘤发生中的作用，以及它们与Akt信号通路相互作用对癌症治疗效果的生物学影响。
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.