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蛋白激酶PIM2:一种在癌症代谢和治疗中具有复杂功能的简单PIM家族激酶。

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics.

作者信息

Wang Yixin, Xiu Jing, Ren Chune, Yu Zhenhai

机构信息

Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, P.R. China.

出版信息

J Cancer. 2021 Mar 5;12(9):2570-2581. doi: 10.7150/jca.53134. eCollection 2021.

Abstract

PIM2 (proviral integration site for Moloney murine leukemia virus 2) kinase plays an important role as an oncogene in multiple cancers, such as leukemia, liver, lung, myeloma, prostate and breast cancers. PIM2 is largely expressed in both leukemia and solid tumors, and it promotes the transcriptional activation of genes involved in cell survival, cell proliferation, and cell-cycle progression. Many tumorigenic signaling molecules have been identified as substrates for PIM2 kinase, and a variety of inhibitors have been developed for its kinase activity, including SMI-4a, SMI-16a, SGI-1776, JP11646 and DHPCC-9. Here, we summarize the signaling pathways involved in PIM2 kinase regulation and PIM2 mechanisms in various neoplastic diseases. We also discuss the current status and future perspectives for the development of PIM2 kinase inhibitors to combat human cancer, and PIM2 will become a therapeutic target in cancers in the future.

摘要

PIM2(莫洛尼鼠白血病病毒2原病毒整合位点)激酶作为一种癌基因在多种癌症中发挥重要作用,如白血病、肝癌、肺癌、骨髓瘤、前列腺癌和乳腺癌。PIM2在白血病和实体瘤中均大量表达,它促进参与细胞存活、细胞增殖和细胞周期进程的基因的转录激活。许多致瘤信号分子已被确定为PIM2激酶的底物,并且已经开发出多种针对其激酶活性的抑制剂,包括SMI-4a、SMI-16a、SGI-1776、JP11646和DHPCC-9。在此,我们总结了参与PIM2激酶调控的信号通路以及PIM2在各种肿瘤性疾病中的作用机制。我们还讨论了开发PIM2激酶抑制剂以对抗人类癌症的现状和未来前景,并且PIM2在未来将成为癌症的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3c9/8040705/43bf54a8f0c1/jcav12p2570g001.jpg

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