Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3517 Cullen Boulevard, Houston, Texas 77204, USA.
Molecular Medicine Program, The Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, USA.
Nat Rev Urol. 2017 Mar;14(3):164-180. doi: 10.1038/nrurol.2016.272. Epub 2017 Feb 1.
The 5'-AMP-activated protein kinase (AMPK) is a master regulator of cellular homeostasis. Despite AMPK's known function in physiology, its role in pathological processes such as prostate cancer is enigmatic. However, emerging evidence is now beginning to decode the paradoxical role of AMPK in cancer and, therefore, inform clinicians if - and how - AMPK could be therapeutically targeted. Spatiotemporal regulation of AMPK complexes could be one of the mechanisms that governs this kinase's role in cancer. We hypothesize that different upstream stimuli will activate select subcellular AMPK complexes. This hypothesis is supported by the distinct subcellular locations of the various AMPK subunits. Each of these unique AMPK complexes regulates discrete downstream processes that can be tumour suppressive or oncogenic. AMPK's final biological output is then determined by the weighted net function of these downstream signalling events, influenced by additional prostate-specific signalling.
5'- 腺苷酸活化蛋白激酶 (AMPK) 是细胞内稳态的主要调节因子。尽管 AMPK 的生理功能已被广泛研究，但它在前列腺癌等病理过程中的作用仍不明确。然而，新出现的证据现在开始揭示 AMPK 在癌症中的矛盾作用，并因此告知临床医生，如果可以的话，AMPK 如何进行治疗性靶向。AMPK 复合物的时空调节可能是控制该激酶在癌症中作用的机制之一。我们假设不同的上游刺激将激活特定的细胞内 AMPK 复合物。这一假设得到了不同 AMPK 亚基的独特细胞内位置的支持。这些独特的 AMPK 复合物中的每一个都调节离散的下游过程，这些过程可能具有肿瘤抑制或致癌作用。AMPK 的最终生物学输出取决于这些下游信号事件的加权净功能，受额外的前列腺特异性信号的影响。
