Popovics Petra, Frigo Daniel E, Schally Andrew V, Rick Ferenc G
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education , Research (151) 2A127, 1201 NW 16th St, Miami, FL 33125 , USA +1 305 5753477 ; +1 305 5753126 ;
Expert Opin Ther Targets. 2015 May;19(5):617-32. doi: 10.1517/14728222.2015.1005603. Epub 2015 Jan 20.
Increasing evidence suggests that prostate cancer cells undergo unique metabolic reprogramming during transformation. A master regulator of cellular homeostasis, 5'-AMP-activated protein kinase (AMPK), directs metabolic adaptation that supports the growth demands of rapidly dividing cancer cells. The utilization of AMPK as a therapeutic target may therefore provide an effective strategy in the treatment of prostate cancer.
Our review describes the regulation of AMPK by androgens and upstream kinases including the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in prostate cancer. Oncogenic, AMPK-regulated pathways that direct various metabolic processes are also addressed. Furthermore, we discuss the role of AMPK in growth arrest and autophagy as a potential survival pathway for cancer cells. In addition, by regulating non-metabolic pathways, AMPK may stimulate migration and mitosis. Finally, this review summarizes efforts to treat prostate cancer with pharmacological agents capable of modulating AMPK signaling.
Current research is primarily focused on developing drugs that activate AMPK as a treatment for prostate cancer. However, oncogenic aspects of AMPK signaling calls for caution about employing such therapies. We think that inhibitors of CaMKK2 or AMPK, or perhaps the modulation of downstream targets of AMPK, will gain importance in the clinical management of prostate cancer.
越来越多的证据表明，前列腺癌细胞在转化过程中会经历独特的代谢重编程。细胞稳态的主要调节因子5'-AMP激活蛋白激酶（AMPK）指导代谢适应，以支持快速分裂的癌细胞的生长需求。因此，将AMPK用作治疗靶点可能为前列腺癌的治疗提供一种有效策略。
我们的综述描述了前列腺癌中雄激素和上游激酶（包括钙/钙调蛋白依赖性蛋白激酶激酶2，CaMKK2）对AMPK的调节。还讨论了指导各种代谢过程的致癌性AMPK调节途径。此外，我们讨论了AMPK在生长停滞和自噬中的作用，这是癌细胞的一种潜在生存途径。此外，通过调节非代谢途径，AMPK可能会刺激迁移和有丝分裂。最后，本综述总结了使用能够调节AMPK信号的药物治疗前列腺癌的研究进展。
目前的研究主要集中在开发激活AMPK的药物来治疗前列腺癌。然而，AMPK信号的致癌方面要求在采用此类疗法时谨慎行事。我们认为，CaMKK2或AMPK的抑制剂，或者对AMPK下游靶点的调节，将在前列腺癌的临床管理中变得更加重要。
