A spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer.
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.
Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3517 Cullen Boulevard, Houston, Texas 77204, USA.
Ayesha S
AS
Khan
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.
Daniel E
DE
Frigo
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D020536:Enzyme Activators / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D014408:Biomarkers, Tumor; D020536:Enzyme Activators; D055372:AMP-Activated Protein Kinases