The multifaceted activities of AMPK in tumor progression - Why the "one size fits all" definition does not fit at all?

IUBMB Life

Volumn 65, Issue 11, 2013, Pages 889-896

  Bonini, Marcelo G ^a   Gantner, Benjamin N ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

AMPK; complex diseases; metformin; nutrient deprivation; signaling; stress activated signaling

Indexed keywords

ADENOSINE TRIPHOSPHATE; CYTOCHROME C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; PROTEIN BCL 2; PROTEIN P53; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE; ROTENONE; SIRTUIN 3; SURVIVIN; APOPTOSIS REGULATORY PROTEIN; PROTEIN KINASE B; TUMOR SUPPRESSOR PROTEIN;

ANTINEOPLASTIC ACTIVITY; CANCER CELL CULTURE; CANCER GROWTH; CANCER STEM CELL; DRUG EFFECT; DRUG INHIBITION; ENZYME ACTIVATION; ENZYME ACTIVITY; EPITHELIAL MESENCHYMAL TRANSITION; MALIGNANT TRANSFORMATION; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATIVE STRESS; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; UPREGULATION; APOPTOSIS; CELL TRANSFORMATION; DISEASE COURSE; DRUG EFFECTS; GLYCOLYSIS; HUMAN; METABOLISM; MITOCHONDRION; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; TUMOR CELL LINE;

AMP-ACTIVATED PROTEIN KINASES; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL LINE, TUMOR; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; ENZYME ACTIVATION; EPITHELIAL-MESENCHYMAL TRANSITION; GLYCOLYSIS; HUMANS; METFORMIN; MITOCHONDRIA; NEOPLASMS; NEOPLASTIC STEM CELLS; PROTO-ONCOGENE PROTEINS C-AKT; TUMOR SUPPRESSOR PROTEINS;

EID: 84888419827     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.1213     Document Type: Review

References (84)

1. Carling, D., Thornton, C., Woods, A., and, Sanders, M. J., (2012) AMP-activated protein kinase: new regulation, new roles? Biochem J 445, 11-27.
2. Eil, C., and, Wool, I. G., (1971) Phosphorylation of rat liver ribosomal subunits: partial purification of two cyclic AMP activated protein kinases. Biochem Biophys Res Commun 43, 1001-1009.
3. Woods, A., Munday, M. R., Scott, J., Yang, X., Carlson, M., et al. (1994) Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem 269, 19509-19515.
4. Carling, D., Aguan, K., Woods, A., Verhoeven, A. J., Beri, R. K., et al. (1994) Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. J Biol Chem 269, 11442-11448.
5. Mitchelhill, K. I., Stapleton, D., Gao, G., House, C., Michell, B., et al. (1994) Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J Biol Chem 269, 2361-2364.
6. Page, K., and, Lange, Y., (1997) Cell adhesion to fibronectin regulates membrane lipid biosynthesis through 5'-AMP-activated protein kinase. J Biol Chem 272, 19339-19342.
7. Muoio, D. M., Seefeld, K., Witters, L. A., and, Coleman, R. A., (1999) AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem J 338, 783-791.
8. Henin, N., Vincent, M. F., Gruber, H. E., Van den Berghe, G., (1995) Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase. FASEB J 9, 541-546.
9. Makinde, A. O., Gamble, J., and, Lopaschuk, G. D., (1997) Upregulation of 5'-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res 80, 482-489.
10. Bergeron, R., Russell, R. R., III, Young, L. H., Ren, J. M., Marcucci, M., et al. (1999) Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 276, E938-944.
11. Kurth-Kraczek, E. J., Hirshman, M. F., Goodyear, L. J., and, Winder, W. W., (1999) 5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48, 1667-1671.
12. Hayashi, T., Hirshman, M. F., Fujii, N., Habinowski, S. A., Witters, L. A., et al. (2000) Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49, 527-531.
13. Fryer, L. G., Hajduch, E., Rencurel, F., Salt, I. P., Hundal, H. S., et al. (2000) Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase. Diabetes 49, 1978-1985.
14. Young, M. E., Radda, G. K., and, Leighton, B., (1996) Activation of glycogen phosphorylase and glycogenolysis in rat skeletal muscle by AICAR-an activator of AMP-activated protein kinase. FEBS Lett 382, 43-47.
15. Almeida, A., Moncada, S., and, Bolanos, J. P., (2004) Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2- kinase pathway. Nat Cell Biol 6, 45-51.
16. Salt, I. P., Johnson, G., Ashcroft, S. J., and, Hardie, D. G., (1998) AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release. Biochem J 335, 533-539.
17. Bolster, D. R., Crozier, S. J., Kimball, S. R., and, Jefferson, L. S., (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277, 23977-23980.
18. Hahn-Windgassen, A., Nogueira, V., Chen, C. C., Skeen, J. E., Sonenberg, N., et al. (2005) Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem 280, 32081-32089.
19. Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., et al. (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36, 585-595.
20. Meley, D., Bauvy, C., Houben-Weerts, J. H., Dubbelhuis, P. F., Helmond, M. T., et al. (2006) AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem 281, 34870-34879.
21. Gallagher, E. J., and, LeRoith, D., (2011) Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci 1243, 54-68.
22. Batandier, C., Guigas, B., Detaille, D., El-Mir, M. Y., Fontaine, E., et al. (2006) The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr 38, 33-42.
23. Stephenne, X., Foretz, M., Taleux, N., van der Zon, G. C., Sokal, E., et al. (2011) Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia 54, 3101-3110.
24. Sauer, H., Engel, S., Milosevic, N., Sharifpanah, F., and, Wartenberg, M., (2012) Activation of AMP-kinase by AICAR induces apoptosis of DU-145 prostate cancer cells through generation of reactive oxygen species and activation of c-Jun N-terminal kinase. Int J Oncol 40, 501-508.
25. Guigas, B., Bertrand, L., Taleux, N., Foretz, M., Wiernsperger, N., et al. (2006) 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. Diabetes 55, 865-874.
26. Santidrian, A. F., Gonzalez-Girones, D. M., Iglesias-Serret, D., Coll-Mulet, L., Cosialls, A. M., et al. (2010) AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood 116, 3023-3032.
27. Garcia-Garcia, C., Fumarola, C., Navaratnam, N., Carling, D., and, Lopez-Rivas, A., (2010) AMPK-independent down-regulation of cFLIP and sensitization to TRAIL-induced apoptosis by AMPK activators. Biochem Pharmacol 79, 853-863.
28. Vucicevic, L., Misirkic, M., Janjetovic, K., Harhaji-Trajkovic, L., Prica, M., et al. (2009) AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. Biochem Pharmacol 77, 1684-1693.
29. Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., et al. (2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A 101, 3329-3335.
30. Shaw, M. M., Gurr, W. K., McCrimmon, R. J., Schorderet, D. F., and, Sherwin, R. S., (2007) 5'AMP-activated protein kinase alpha deficiency enhances stress-induced apoptosis in BHK and PC12 cells. J Cell Mol Med 11, 286-298.
31. Chhipa, R. R., Wu, Y., Mohler, J. L., Ip, C., (2010) Survival advantage of AMPK activation to androgen-independent prostate cancer cells during energy stress. Cell Signal 22, 1554-1561.
32. Matsui, Y., Takagi, H., Qu, X., Abdellatif, M., Sakoda, H., et al. (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100, 914-922.
33. Zarrinpashneh, E., Carjaval, K., Beauloye, C., Ginion, A., Mateo, P., et al. (2006) Role of the alpha2-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia. Am J Physiol Heart Circ Physiol 291, H2875-2883.
34. Wang, S., Song, P., and, Zou, M. H., (2012) Inhibition of AMP-activated protein kinase alpha (AMPKalpha) by doxorubicin accentuates genotoxic stress and cell death in mouse embryonic fibroblasts and cardiomyocytes: role of p53 and SIRT1. J Biol Chem 287, 8001-8012.
35. Liu, C., Liang, B., Wang, Q., Wu, J., and, Zou, M. H., (2010) Activation of AMP-activated protein kinase alpha1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins Bcl-2 and survivin. J Biol Chem 285, 15346-15355.
36. Kawasaki, H., Altieri, D. C., Lu, C. D., Toyoda, M., Tenjo, T., et al. (1998) Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 58, 5071-5074.
37. Hinnis, A. R., Luckett, J. C., and, Walker, R. A., (2007) Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients. Br J Cancer 96, 639-645.
38. Dole, M., Nunez, G., Merchant, A. K., Maybaum, J., Rode, C. K., et al. (1994) Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma. Cancer Res 54, 3253-3259.
39. Piris, M. A., Pezzella, F., Martinez-Montero, J. C., Orradre, J. L., Villuendas, R., et al. (1994) p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time. Br J Cancer 69, 337-341.
40. Kato, K., Ogura, T., Kishimoto, A., Minegishi, Y., Nakajima, N., et al. (2002) Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene 21, 6082-6090.
41. Ng, T. L., Leprivier, G., Robertson, M. D., Chow, C., Martin, M. J., et al. (2012) The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death Differ 19, 501-510.
42. Zakikhani, M., Bazile, M., Hashemi, S., Javeshghani, S., Avizonis, D., et al. (2012) Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin. PLoS One 7, e49513.
43. Owen, M. R., Doran, E., and, Halestrap, A. P., (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348, 607-614.
44. Ben Sahra, I., Regazzetti, C., Robert, G., Laurent, K., Le Marchand-Brustel, Y., et al. (2011) Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res 71, 4366-4372.
45. Buler, M., Aatsinki, S. M., Izzi, V., and, Hakkola, J., (2012) Metformin reduces hepatic expression of SIRT3, the mitochondrial deacetylase controlling energy metabolism. PLoS One 7, e49863.
46. Tao, R., Coleman, M. C., Pennington, J. D., Ozden, O., Park, S. H., et al. (2010) Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40, 893-904.
47. Ouyang, J., Parakhia, R. A., and, Ochs, R. S., (2011) Metformin activates AMP kinase through inhibition of AMP deaminase. J Biol Chem 286, 1-11.
48. Jeon, S. M., Chandel, N. S., and, Hay, N., (2012) AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661-665.
49. Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-1322.
50. Hsu, P. P., and, Sabatini, D. M., (2008) Cancer cell metabolism: warburg and beyond. Cell 134, 703-707.
51. Shackelford, D. B., and, Shaw, R. J., (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 9, 563-575.
52. Shaw, R. J., (2009) Tumor suppression by LKB1: SIK-ness prevents metastasis. Sci Signal 2, pe55.
53. 53., Massie, C. E., Lynch, A., Ramos-Montoya, A., Boren, J., Stark, R., et al. (2011) The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. EMBO J 30, 2719-2733. DOI: 10.1186/1742-2094-10-58.
54. Frigo, D. E., Howe, M. K., Wittmann, B. M., Brunner, A. M., Cushman, I., et al. (2011) CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells. Cancer Res 71, 528-537.
55. Martinez-Reyes, I., Sanchez-Arago, M., and, Cuezva, J. M., (2012) AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells. Biochem J 444, 249-259.
56. Hay, N., (2005) The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8, 179-183.
57. King, T. D., Song, L., and, Jope, R. S., (2006) AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3. Biochem Pharmacol 71, 1637-1647.
58. Leclerc, G. M., Leclerc, G. J., Fu, G., and, Barredo, J. C., (2010) AMPK-induced activation of Akt by AICAR is mediated by IGF-1R dependent and independent mechanisms in acute lymphoblastic leukemia. J Mol Signal 5, 15.
59. Tao, R., Gong, J., Luo, X., Zang, M., Guo, W., et al. (2010) AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal 5, 1.
60. Zoncu, R., Efeyan, A., and, Sabatini, D. M., (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12, 21-35.
61. Easton, J. B., Kurmasheva, R. T., and, Houghton, P. J., (2006) IRS-1: auditing the effectiveness of mTOR inhibitors. Cancer Cell 9, 153-155.
62. Wan, X., Harkavy, B., Shen, N., Grohar, P., and, Helman, L. J., (2007) Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 26, 1932-1940.
63. Soares, H. P., Ni, Y., Kisfalvi, K., Sinnett-Smith, J., and, Rozengurt, E., (2013) Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells. PLoS One 8, e57289.
64. Ward, P. S., and, Thompson, C. B., (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21, 297-308.
65. Bendall, S. C., and, Nolan, G. P., (2012) From single cells to deep phenotypes in cancer. Nat Biotechnol 30, 639-647.
66. Hanahan, D., and, Coussens, L. M., (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309-322.
67. Yamanaka, S., and, Blau, H. M., (2010) Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704-712.
68. Li, R., Liang, J., Ni, S., Zhou, T., Qing, X., et al. (2010) A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7, 51-63.
69. Wang, X., Pan, X., and, Song, J., (2010) AMP-activated protein kinase is required for induction of apoptosis and epithelial-to-mesenchymal transition. Cell Signal 22, 1790-1797.
70. Vazquez-Martin, A., Vellon, L., Quiros, P. M., Cufi, S., Ruiz de Galarreta, E., et al. (2012) Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells. Cell Cycle 11, 974-989.
71. Liu, W., Long, Q., Chen, K., Li, S., Xiang, G., et al. (2013) Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation. Biochem Biophys Res Commun 431, 767-771.
72. Tello, D., Balsa, E., Acosta-Iborra, B., Fuertes-Yebra, E., Elorza, A., et al. (2011) Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab 14, 768-779.
73. Mauro, C., Leow, S. C., Anso, E., Rocha, S., Thotakura, A. K., et al. (2011) NF-kappaB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. Nat Cell Biol 13, 1272-1279.
74. Folmes, C. D., Martinez-Fernandez, A., Faustino, R. S., Yamada, S., Perez-Terzic, C., et al. (2013) Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells. J Cardiovasc Transl Res 6, 10-21.
75. Panopoulos, A. D., Yanes, O., Ruiz, S., Kida, Y. S., Diep, D., et al. (2012) The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res 22, 168-177.
76. Rios, M., Foretz, M., Viollet, B., Prieto, A., Fraga, M., et al. AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors. Cancer Res, in press.
77. Rodriguez-Jimnez, F. J., Alastrue-Agudo, A., Erceg, S., Stojkovic, M., and, Moreno-Manzano, V., (2012) FM19G11 favors spinal cord injury regeneration and stem cell self-renewal by mitochondrial uncoupling and glucose metabolism induction. Stem Cells 30, 2221-2233.
78. Suzuki, A., Lu, J., Kusakai, G., Kishimoto, A., Ogura, T., et al. (2004) ARK5 is a tumor invasion-associated factor downstream of Akt signaling. Mol Cell Biol 24, 3526-3535.
79. Liu, L., Ulbrich, J., Muller, J., Wustefeld, T., Aeberhard, L., et al. (2012) Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature 483, 608-612.
80. Menendez, J. A., Vellon, L., Oliveras-Ferraros, C., Cufi, S., and, Vazquez-Martin, A., (2011) mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency: a roadmap from energy metabolism to stem cell renewal and aging. Cell Cycle 10, 3658-3677.
81. Ge, W., and, Ren, J., (2012) mTOR-STAT3-notch signalling contributes to ALDH2-induced protection against cardiac contractile dysfunction and autophagy under alcoholism. J Cell Mol Med 16, 616-626.
82. Zeve, D., Seo, J., Suh, J. M., Stenesen, D., Tang, W., et al. (2012) Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. Cell Metab 15, 492-504.
83. Xie, Y., Awonuga, A., Liu, J., Rings, E., Puscheck, E. E., et al. Stress induces AMP-activated protein kinase-dependent loss of potency factors inhibitor of differentiation 2 and caudal-related homeodomain protein 2 in early embryos and stem cells. Stem Cells Dev, in press.
84. Pantovic, A., Krstic, A., Janjetovic, K., Kocic, J., Harhaji-Trajkovic, L., et al. (2013) Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. Bone 52, 524-531.