The Role of Energy Metabolism in Driving Disease Progression in Inflammatory, Hypoxic and Angiogenic Microenvironments

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Authors

  • James J. Phelan Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland
  • C. O’Hanlon Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland
  • John V. Reynolds Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland
  • Jacintha O’Sullivan Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland

DOI:

https://doi.org/10.17140/GOJ-1-108

Keywords:

Energy metabolism, Inflammation, Hypoxia, Angiogenesis

Abstract

Cellular metabolism plays a crucial role in primed inflammatory, hypoxic and angiogenic microenvironments by supporting disease progression in a range of disease entities. To adapt to fluctuating stress-induced microenvironments, pre-neoplastic and neoplastic tissue must utilise a diverse range of molecular mediators to alter their metabolism. Despite being widely documented to play independent roles in disease prevalence, these complex processes exploit a range of key cellular components that act in tandem to restore metabolic equilibrium. Therefore, this review examines the primary molecular mechanisms linking energy metabolism with inflammation, hypoxia and angiogenesis. Furthermore, the review considers a diverse range of conventional and novel mediators that link energy metabolism and hypoxia. More over, to investigate their reciprocal relationship and the mechanisms employed to execute their functional effect in greater detail, the roles of glycolysis and oxidative phosphorylation in rheumatoid arthritis and circadian rhythms respectively are reviewed. Lastly, this review explores some current metabolic-based treatments and multi-targeted therapies that could potentially target these fundamental cellular processes.

References

Warburg O. On the origin of cancer cells. Science. 1956; 123(3191): 309-314. doi: 10.1126/science.123.3191.309

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1): 57-70. doi: 10.1016/S0092-8674(00)81683-9

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-674. doi: 10.1016/j. cell.2011.02.013

Weinberg F, Chandel NS. Mitochondrial metabolism and can-cer. Annals of the New York Academy of Sciences. 2009; 1177: 66-73. doi: 10.1111/j.1749-6632.2009.05039.x

Tennant DA, Duran RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nature reviews Cancer. 2010; 10(4): 267-277. doi: 10.1038/nrc2817

Ling FC, Khochfar J, Baldus SE, et al. HIF-1alpha protein expression is associated with the environmental inflammatory reaction in Barrett’s metaplasia. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / ISDE. 2009; 22(8): 694-699. doi: 10.1111/j.1442- 2050.2009.00957.x

Schmaltz C, Hardenbergh PH, Wells A, Fisher DE. Regulation of proliferation-survival decisions during tumor cell hypoxia. Molecular and cellular biology. 1998; 18(5): 2845-2854.

Brizel DM, Scully SP, Harrelson JM, et al. Tumor oxygen-ation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer research. 1996; 56(5): 941-943.

Casey TM, Pakay JL, Guppy M, Arthur PG. Hypoxia causes downregulation of protein and RNA synthesis in noncontracting Mammalian cardiomyocytes. Circulation research. 2002; 90(7): 777-783. doi: 10.1161/01.RES.0000015592.95986.0

Semenza GL. Regulation of metabolism by hypoxia-induc-ible factor 1. Cold Spring Harbor symposia on quantitative biol-ogy. 2011; 76: 347-353. doi: 10.1101/sqb.2011.76.010678

Zheng Y, Delgoffe GM, Meyer CF, Chan W, Powell JD. An-ergic T cells are metabolically anergic. Journal of immunology. 2009; 183(10): 6095-6101. doi: 10.4049/jimmunol.0803510

Fox CJ, Hammerman PS, Thompson CB. Fuel feeds func-tion: energy metabolism and the T-cell response. Nature reviews Immunology. 2005; 5(11): 844-852. doi: 10.1038/nri1710

Dziurla R, Gaber T, Fangradt M, et al. Effects of hypoxia and/or lack of glucose on cellular energy metabolism and cy-tokine production in stimulated human CD4+ T lymphocytes. Immunology letters. 2010; 131(1): 97-105. doi: 10.1016/j. imlet.2010.02.008

Dang EV, Barbi J, Yang HY, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011; 146(5): 772- 784. doi: 10.1016/j.cell.2011.07.033

Shi LZ, Wang R, Huang G, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. The Journal of ex-perimental medicine. 2011; 208(7): 1367-1376. doi: 10.1084/ jem.20110278

Finlay DK, Rosenzweig E, Sinclair LV, et al. PDK1 regu-lation of mTOR and hypoxia-inducible factor 1 integrate me-tabolism and migration of CD8+ T cells. The Journal of ex-perimental medicine. 2012; 209(13): 2441-2453. doi: 10.1084/ jem.20112607

Dandapani M, Hardie DG. AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? Biochemi-cal Society Transactions. 2013; 41(2): 687-693. doi: 10.1042/ BST20120351

Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA ribo-side increases AMP-activated protein kinase, fatty acid oxida-tion, and glucose uptake in rat muscle. The American Journal of Physiology. 1997; 273(6 Pt 1): E1107-E1112.

Zong H, Ren JM, Young LH, et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings of the National Acad-emy of Sciences of the United States of America. 2002; 99(25): 15983-15987. doi: 10.1073/pnas.252625599

Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO. Activation of AMP-activated protein kinase in-creases mitochondrial enzymes in skeletal muscle. Journal of applied physiology (Bethesda, Md : 1985). 2000; 88(6): 2219- 2226.

Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and en-ergy sensor that maintains energy homeostasis. Nature reviews Molecular cell biology. 2012; 13(4): 251-262. doi: 10.1038/ nrm3311

Hoppe S, Bierhoff H, Cado I, et al. AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Pro-ceedings of the National Academy of Sciences of the United States of America. 2009; 106(42): 17781-17786. doi: 10.1073/ pnas.0909873106

Shackelford DB, Vasquez DS, Corbeil J, et al. mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proceedings of the Nation-al Academy of Sciences of the United States of America. 2009; 106(27): 11137-11142. doi: 10.1073/pnas.0900465106

Krawczyk CM, Holowka T, Sun J, et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood. 2010; 115(23): 4742-4749. doi: 10.1182/ blood-2009-10-249540

Sag D, Carling D, Stout RD, Suttles J. Adenosine 5’-mono-phosphate-activated protein kinase promotes macrophage polar-ization to an anti-inflammatory functional phenotype. Journal of immunology (Baltimore, Md : 1950). 2008; 181(12): 8633-8641. doi: 10.4049/jimmunol.181.12.8633

Rolf J, Zarrouk M, Finlay DK, Foretz M, Viollet B, Cantrell DA. AMPKalpha1: a glucose sensor that controls CD8 T-cell memory. European journal of immunology. 2013; 43(4): 889- 896. doi: 10.1002/eji.201243008

Berkers CR, Maddocks OD, Cheung EC, Mor I, Vousden KH. Metabolic regulation by p53 family members. Cell Metabo-lism. 2013; 18(5): 617-633. doi: 10.1016/j.cmet.2013.06.019

Vousden KH, Ryan KM. p53 and metabolism. Nature re-views Cancer. 2009; 9(10): 691-700. doi: 10.1038/nrc2715

Kulawiec M, Ayyasamy V, Singh KK. p53 regulates mtDNA copy number and mitocheckpoint pathway. Journal of carcino-genesis. 2009; 8: 8. doi: 10.4103/1477-3163.50893

Sahin E, Colla S, Liesa M, et al. Telomere dysfunction in-duces metabolic and mitochondrial compromise. Nature. 2011; 470(7334): 359-365. doi: 10.1038/nature09787

Kitamura N, Nakamura Y, Miyamoto Y, et al. Mieap, a p53- inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. PLoS One. 2011; 6(1): e16060. doi: 10.1371/journal.pone.0016060

Cardin R, Piciocchi M, Tieppo C, et al. Oxidative DNA dam-age in Barrett mucosa: correlation with telomeric dysfunction and p53 mutation. Annals of surgical oncology. 2013; 20 Suppl 3: S583-S589. doi: 10.1245/s10434-013-3043-1

Matoba S, Kang JG, Patino WD, et al. p53 regulates mi-tochondrial respiration. Science. 2006; 312(5780): 1650-1653. doi: 10.1126/science.1126863

Okamura S, Ng CC, Koyama K, et al. Identification of seven genes regulated by wild-type p53 in a colon cancer cell line car-rying a well-controlled wild-type p53 expression system. Oncol-ogy research. 1999; 11(6): 281-285.

Stambolsky P, Weisz L, Shats I, et al. Regulation of AIF ex-pression by p53. Cell death and differentiation. 2006; 13(12): 2140-2149. doi: 10.1038/sj.cdd.4401965

Cheung EC, Ludwig RL, Vousden KH. Mitochondrial lo-calization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(50): 20491- 20496. doi: 10.1073/pnas.1206530109

Li H, Jogl G. Structural and biochemical studies of TIGAR (TP53-induced glycolysis and apoptosis regulator). The Journal of biological chemistry. 2009; 284(3): 1748-1754. doi: 10.1074/ jbc.M807821200

Contractor T, Harris CR. p53 negatively regulates tran-scription of the pyruvate dehydrogenase kinase Pdk2. Cancer research. 2012; 72(2): 560-567. doi: 10.1158/0008-5472.CAN-11-1215

Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer research. 2004; 64(7): 2627-2633. doi: 10.1158/0008-5472.CAN-03-0846

Boidot R, Vegran F, Meulle A, et al. Regulation of monocar-boxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer research. 2012; 72(4): 939-948. doi: 10.1158/0008-5472.CAN-11-2474

Mathupala SP, Heese C, Pedersen PL. Glucose catabolism in cancer cells. The type II hexokinase promoter contains function-ally active response elements for the tumor suppressor p53. The Journal of biological chemistry. 1997; 272(36): 22776-22780. doi: 10.1074/jbc.272.36.22776

Maddocks OD, Vousden KH. Metabolic regulation by p53. Journal of molecular medicine (Berlin, Germany). 2011; 89(3): 237-245. doi: 10.1007/s00109-011-0735-5

Hotamisligil GS, Erbay E. Nutrient sensing and inflamma-tion in metabolic diseases. Nature reviews Immunology. 2008; 8(12): 923-934. doi: 10.1038/nri2449

Solinas G, Karin M. JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010; 24(8): 2596-2611. doi: 10.1096/ fj.09-151340

Tornatore L, Thotakura AK, Bennett J, Moretti M, Franzoso G. The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation. Trends in cell biology. 2012; 22(11): 557-566. doi: 10.1016/j.tcb.2012.08.001

Marusawa H, Jenkins BJ. Inflammation and gastrointestinal cancer: an overview. Cancer Letters. 2014; 345(2): 153-156. doi: 10.1016/j.canlet.2013.08.025

DiDonato JA, Mercurio F, Karin M. NF-kappaB and the link between inflammation and cancer. Immunological reviews. 2012; 246(1): 379-400. doi: 10.1111/j.1600-065X.2012.01099.x

Grivennikov SI, Greten FR, Karin M. Immunity, inflamma-tion, and cancer. Cell. 2010; 140(6): 883-899. doi: 10.1016/j. cell.2010.01.025

Johnson RF, Witzel, II, Perkins ND. p53-dependent regu-lation of mitochondrial energy production by the RelA subunit of NF-kappaB. Cancer research. 2011; 71(16): 5588-5597. doi: 10.1158/0008-5472.CAN-10-4252

Kawauchi K, Araki K, Tobiume K, Tanaka N. p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. Nature cell biology. 2008; 10(5): 611-618. doi: 10.1038/ncb1724

Mauro C, Leow SC, Anso E, et al. NF-kappaB controls en-ergy homeostasis and metabolic adaptation by upregulating mi-tochondrial respiration. Nature cell biology. 2011; 13(10): 1272- 1279. doi: 10.1038/ncb2324

Eelen G, Cruys B, Welti J, De Bock K, Carmeliet P. Con-trol of vessel sprouting by genetic and metabolic determinants. Trends in endocrinology and metabolism: TEM. 2013; 24(12): 589-596. doi: 10.1016/j.tem.2013.08.006

De Bock K, Georgiadou M, Carmeliet P. Role of endothe-lial cell metabolism in vessel sprouting. Cell metabolism. 2013; 18(5): 634-647. doi: 10.1016/j.cmet.2013.08.001

De Bock K, Georgiadou M, Schoors S, et al. Role of PFKFB3- driven glycolysis in vessel sprouting. Cell. 2013; 154(3): 651- 663. doi: 10.1016/j.cell.2013.06.037

Potente M, Gerhardt H, Carmeliet P. Basic and therapeu-tic aspects of angiogenesis. Cell. 2011; 146(6): 873-887. doi: 10.1016/j.cell.2011.08.039

Sonveaux P, Copetti T, De Saedeleer CJ, et al. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PLoS One. 2012; 7(3): e33418g. doi: 10.1371/journal.pone.0033418

Hunt TK, Aslam RS, Beckert S, et al. Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxidants & redox signaling. 2007; 9(8): 1115- 1124. doi: 10.1089/ars.2007.1674

Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lac-tate influx through the endothelial cell monocarboxylate trans-porter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Research. 2011; 71(7): 2550-2560. doi: 10.1158/0008-5472.CAN-10-2828

Hao Q, Wang L, Tang H. Vascular endothelial growth factor induces protein kinase D-dependent production of proinflamma-tory cytokines in endothelial cells. American journal of physiol-ogy Cell physiology. 2009; 296(4): C821-C827. doi: 10.1152/ ajpcell.00504.2008

Wright GL, Maroulakou IG, Eldridge J, et al. VEGF stimula-tion of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB journal : official publication of the Federation of Ameri-can Societies for Experimental Biology. 2008; 22(9): 3264-3275. doi: 10.1096/fj.08-106468

Elmasri H, Karaaslan C, Teper Y, et al. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell prolifera-tion in endothelial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2009; 23(11): 3865-3873. doi: 10.1096/fj.09-134882

Hagberg CE, Mehlem A, Falkevall A, et al. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature. 2012; 490(7420): 426-430. doi: 10.1038/na-ture11464

Xu X, Ye L, Araki K, Ahmed R. mTOR, linking metabolism and immunity. Seminars in immunology. 2012; 24(6): 429-435. doi: 10.1016/j.smim.2012.12.005

Thomson AW, Turnquist HR, Raimondi G. Immunoregula-tory functions of mTOR inhibition. Nature reviews Immunology. 2009; 9(5): 324-337. doi: 10.1038/nri2546

Buller CL, Loberg RD, Fan MH, et al.AGSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transport-er expression. American journal of physiology Cell physiology. 2008; 295(3): C836-C843. doi: 10.1152/ajpcell.00554.2007

Duvel K, Yecies JL, Menon S, et al. Activation of a meta-bolic gene regulatory network downstream of mTOR com-plex 1. Molecular cell. 2010; 39(2): 171-183. doi: 10.1016/j. molcel.2010.06.022

Wang R, Dillon CP, Shi LZ, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 2011; 35(6): 871-882. doi: 10.1016/j. immuni.2011.09.021

Araki K, Turner AP, Shaffer VO, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009; 460(7251): 108-112. doi: 10.1038/nature08155

Selak MA, Armour SM, MacKenzie ED, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005; 7(1): 77-85. doi: 10.1016/j.ccr.2004.11.022

Pistollato F, Abbadi S, Rampazzo E, et al. Hypoxia and succinate antagonize 2-deoxyglucose effects on glioblastoma. Biochemical pharmacology. 2010; 80(10): 1517-1527. doi: 10.1016/j.bcp.2010.08.003

Tannahill GM, Curtis AM, Adamik J, et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013; 496(7444): 238-242. doi: 10.1038/nature11986

Qi QR, Yang ZM. Regulation and function of signal trans-ducer and activator of transcription 3. World journal of biological chemistry. 2014; 5(2): 231-239. doi: 10.4331/wjbc.v5.i2.231

Haigis MC, Deng CX, Finley LW, Kim HS, Gius D. SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer research. 2012; 72(10): 2468-2472. doi: 10.1158/0008- 5472.CAN-11-3633

Tateno T, Asa SL, Zheng L, Mayr T, Ullrich A, Ez-zat S. The FGFR4-G388R polymorphism promotes mito-chondrial STAT3 serine phosphorylation to facilitate pitu-itary growth hormone cell tumorigenesis. PLoS genetics. 2011; 7(12): e1002400. doi: 10.1371/journal.pgen.1002400

Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. Mitochondrial STAT3 supports Ras-dependent onco-genic transformation. Science. 2009; 324(5935): 1713-1716. doi: 10.1126/science.1171721

Gough DJ, Marie IJ, Lobry C, Aifantis I, Levy DE. STAT3 supports experimental K-RasG12D-induced murine myelo-proliferative neoplasms dependent on serine phosphorylation. Blood. 2014; 22. doi: 10.1182/blood-2013-02-484196

Henderson B, Bitensky L, Chayen J. Glycolytic activity in human synovial lining cells in rheumatoid arthritis. Annals of the rheumatic diseases. 1979; 38(1): 63-67.

Chang X, Wei C. Glycolysis and rheumatoid arthritis. Inter-national journal of rheumatic diseases. 2011; 14(3): 217-222. doi: 10.1111/j.1756-185X.2011.01598.x

Ciurtin C, Cojocaru VM, Miron IM, et al. Correlation be-tween different components of synovial fluid and pathogenesis of rheumatic diseases. Romanian journal of internal medicine = Revue roumaine de medecine interne. 2006; 44(2): 171-181.

Biniecka M, Fox E, Gao W, et al. Hypoxia induces mitochon-drial mutagenesis and dysfunction in inflammatory arthritis. Ar-thritis and rheumatism. 2011; 63(8): 2172-2182. doi: 10.1002/ art.30395

Moran EM, Heydrich R, Ng CT, et al. IL-17A expression is localised to both mononuclear and polymorphonuclear synovial cell infiltrates. PLoS One. 2011; 6(8): e24048. doi: 10.1371/jour-nal.pone.0024048

Biniecka M, Kennedy A, Ng CT, et al. Successful tumour ne-crosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflamma-tory arthritis. Arthritis research & therapy. 2011; 13(4): R121. doi: 10.1186/ar3424

Kennedy A, Ng CT, Chang TC, et al. Tumor necrosis factor blocking therapy alters joint inflammation and hypoxia. Arthritis and rheumatism. 2011; 63(4): 923-932. doi: 10.1002/art.30221

Ng CT, Biniecka M, Kennedy A, et al. Synovial tissue hy-poxia and inflammation in vivo. Annals of the rheumatic dis-eases. 2010; 69(7): 1389-1395. doi: 10.1136/ard.2009.119776

HollanderAP, Corke KP, FreemontAJ, Lewis CE. Expression of hypoxia-inducible factor 1alpha by macrophages in the rheu-matoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis and rheumatism. 2001; 44(7): 1540-1544. doi: 10.1002/1529-0131(200107)44:7<1540::AID-ART277>3.0.CO;2-7

Giatromanolaki A, Sivridis E, Maltezos E, et al. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheu-matoid arthritis and osteoarthritis. Arthritis research & therapy. 2003; 5(4): R193-R201. doi: 10.1186/ar756

Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA. Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular compo-nents of the oxygen and glucose sensing apparatus in articular chondrocytes. Histology and histopathology. 2005; 20(4): 1327- 1338.

Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! Annals of the rheumatic diseases. 2005; 64(7): 971-980. doi: 10.1136/ard.2004.031641

Bodamyali T, Stevens CR, Billingham ME, Ohta S, Blake DR. Influence of hypoxia in inflammatory synovitis. Annals of the rheumatic diseases. 1998; 57(12): 703-710.

Distler JH, Wenger RH, Gassmann M, et al. Physiologic re-sponses to hypoxia and implications for hypoxia-inducible fac-tors in the pathogenesis of rheumatoid arthritis. Arthritis and rheumatism. 2004; 50(1): 10-23. doi: 10.1002/art.11425

Taylor PC, Sivakumar B. Hypoxia and angiogenesis in rheu-matoid arthritis. Current opinion in rheumatology. 2005; 17(3): 293-298. doi: 10.1097/01.bor.0000155361.83990.5b

Firestein GS, Echeverri F, Yeo M, Zvaifler NJ, Green DR. Somatic mutations in the p53 tumor suppressor gene in rheuma-toid arthritis synovium. Proceedings of the National Academy of Sciences of the United States of America. 1997; 94(20): 10895- 10900. doi: 10.1073/pnas.94.20.10895

Reme T, Travaglio A, Gueydon E, Adla L, Jorgensen C, Sany J. Mutations of the p53 tumour suppressor gene in erosive rheu-matoid synovial tissue. Clinical and experimental immunology. 1998; 111(2): 353-358. doi: 10.1046/j.1365-2249.1998.00508.x

Kullmann F, Judex M, Neudecker I, et al. Analysis of the p53 tumor suppressor gene in rheumatoid arthritis synovial fibro-blasts. Arthritis and rheumatism. 1999; 42(8): 1594-1600. doi: 1 0 . 1 0 0 2 / 1 5 2 9 - 0 1 3 1 ( 1 9 9 9 0 8 ) 4 2 : 8 < 1 5 9 4 : : A I D -ANR5>3.0.CO;2-#

Kawauchi K, Araki K, Tobiume K, Tanaka N. Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(9): 3431-3436. doi: 10.1073/pnas.0813210106

Biniecka M, Connolly M, Gao W, et al. Redox mediated an-giogenesis in the hypoxic joint of inflammatory arthritis. Arthri-tis & rheumatology (Hoboken, NJ). 2014; 66(12): 3300-3310. doi: 10.1002/art.38822

Yang M, Guo M, Hu Y, Jiang Y. Scube regulates synovial an-giogenesis-related signaling. Medical hypotheses. 2013; 81(5): 948-953. doi: 10.1016/j.mehy.2013.09.001

Bailey SM, Udoh US, Young ME. Circadian regulation of metabolism. The Journal of endocrinology. 2014; 222(2): R75- R96. doi: 10.1530/JOE-14-0200

Langmesser S, Albrecht U. Life time-circadian clocks, mi-tochondria and metabolism. Chronobiology international. 2006; 23(1-2): 151-157. doi: 10.1080/07420520500464437

Nikonova EV, Vijayasarathy C, Zhang L, et al. Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness. Sleep. 2005; 28(1): 21-27.

Jordan SD, Lamia KA. AMPK at the crossroads of circa-dian clocks and metabolism. Molecular and cellular endocrinol-ogy. 2013; 366(2): 163-169. doi: 10.1016/j.mce.2012.06.017

Sancar A. Regulation of the mammalian circadian clock by cryptochrome. The Journal of biological chemistry. 2004; 279(33): 34079-34082. doi: 10.1074/jbc.R400016200

Busino L, Bassermann F, Maiolica A, et al. SCFFbxl3 con-trols the oscillation of the circadian clock by directing the deg-radation of cryptochrome proteins. Science. 2007; 316(5826): 900-904. doi: 10.1126/science.1141194

Lamia KA, Sachdeva UM, DiTacchio L, et al. AMPK regu-lates the circadian clock by cryptochrome phosphorylation and degradation. Science. 2009; 326(5951): 437-440. doi: 10.1126/ science.1172156

Etchegaray JP, Machida KK, Noton E, et al. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Molecular and cellular biology. 2009; 29(14): 3853-3866. doi: 10.1128/MCB.00338-09

Um JH, Yang S, Yamazaki S, et al. Activation of 5’-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem. 2007; 282(29): 20794-20798. doi: 10.1074/jbc.C700070200

Vieira E, Nilsson EC, Nerstedt A, et al. Relationship be-tween AMPK and the transcriptional balance of clock-related genes in skeletal muscle. American journal of physiology En-docrinology and metabolism. 2008; 295(5): E1032-E1037. doi: 10.1152/ajpendo.90510.2008

Canto C, Gerhart-Hines Z, Feige JN, et al. AMPK regu-lates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009; 458(7241): 1056-1060. doi: 10.1038/nature07813

Lan F, Cacicedo JM, Ruderman N, Ido Y. SIRT1 modula-tion of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activa-tion. The Journal of biological chemistry. 2008; 283(41): 27628- 27635. doi: 10.1074/jbc.M805711200

Walker JW, Jijon HB, Madsen KL. AMP-activated protein kinase is a positive regulator of poly(ADP-ribose) polymerase. Biochemical and biophysical research communications. 2006; 342(1): 336-341. doi: 10.1016/j.bbrc.2006.01.145

Fulco M, Cen Y, Zhao P, et al. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Developmental cell. 2008; 14(5): 661-673. doi: 10.1016/j.devcel.2008.02.004

Zhang X, Xu L, Shen J, et al. Metabolic signatures of esophageal cancer: NMR-based metabolomics and UHPLC-based focused metabolomics of blood serum. Biochimica et biophysica acta. 2013; 1832(8): 1207-1216. doi: 10.1016/j. bbadis.2013.03.009

Abbassi-Ghadi N, Kumar S, Huang J, Goldin R, Takats Z, Hanna GB. Metabolomic profiling of oesophago-gastric cancer: a systematic review. European journal of cancer. 2013; 49(17): 3625-3637. doi: 10.1016/j.ejca.2013.07.004

Ussakli CH, Ebaee A, Binkley J, et al. Mitochondria and tumor progression in ulcerative colitis. Journal of the National Cancer Institute. 2013; 105(16): 1239-1248. doi: 10.1093/jnci/ djt167

Gruno M, Peet N, Tein A, et al. Atrophic gastritis: deficient complex I of the respiratory chain in the mitochondria of corpus mucosal cells. Journal of gastroenterology. 2008; 43(10): 780- 788. doi: 10.1007/s00535-008-2231-4

O’Sullivan KE, Phelan JJ, O’Hanlon C, Lysaght J, O’Sullivan JN, Reynolds JV. The role of inflammation in cancer of the esophagus. Expert review of gastroenterology & hepatol-ogy. 2014; 8(7): 749-760. doi: 10.1586/17474124.2014.913478

Phelan JJ, MacCarthy F, Feighery R, et al. Differential ex-pression of mitochondrial energy metabolism profiles across the metaplasia-dysplasia-adenocarcinoma disease sequence in Bar-rett’s oesophagus. Cancer Letters. 2014; 354(1): 122-131. doi: 10.1016/j.canlet.2014.07.035

Ando M, Uehara I, Kogure K, et al. Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexo-kinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bispho-sphatase-3. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi. 2010; 77(2): 97-105. doi: 10.1272/jnms.77.97

Catarzi S, Favilli F, Romagnoli C, et al. Oxidative state and IL-6 production in intestinal myofibroblasts of Crohn’s disease patients. Inflammatory bowel diseases. 2011; 17(8): 1674-1684. doi: 10.1002/ibd.21552

Dvorakova K, Payne CM, Ramsey L, et al. Increased ex-pression and secretion of interleukin-6 in patients with Barrett’s esophagus. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004; 10(6): 2020- 2028. doi: 10.1158/1078-0432.CCR-0437-03

Kastelein F, Biermann K, Steyerberg EW, et al. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett’s oesophagus. Gut. 2013; 62(12): 1676-1683. doi: 10.1136/gutjnl-2012-30359

Angelo LS, Talpaz M, Kurzrock R. Autocrine interleukin-6 production in renal cell carcinoma: evidence for the involvement of p53. Cancer research. 2002; 62(3): 932-940.

Bar F, Bochmann W, Widok A, et al. Mitochondrial gene polymorphisms that protect mice from colitis. Gastroenterology. 2013; 145(5): 1055e3-1063e3. doi: 10.1053/j.gastro.2013.07.015

Gruno M, Peet N, Seppet E, et al. Oxidative phosphory-lation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa. American journal of physiol-ogy Regulatory, integrative and comparative physiology. 2006; 291(4): R936-R946. doi: 10.1152/ajpregu.00162.2006

Puurand M, Peet N, Piirsoo A, et al. Deficiency of the complex I of the mitochondrial respiratory chain but improved adenylate control over succinate-dependent respiration are hu-man gastric cancer-specific phenomena. Molecular and cellular biochemistry. 2012; 370(1-2): 69-78. doi: 10.1007/s11010-012- 1399-3

Chan AW, Gill RS, Schiller D, Sawyer MB. Potential role of metabolomics in diagnosis and surveillance of gastric cancer. World journal of gastroenterology : WJG. 2014; 20(36): 12874- 12882. doi: 10.3748/wjg.v20.i36.12874

Li H, Wang J, Xu H, et al. Decreased fructose-1,6-bispho-sphatase-2 expression promotes glycolysis and growth in gas-tric cancer cells. Molecular cancer. 2013; 12(1): 110. doi: 10.1186/1476-4598-12-110

Liu X, Wang X, Zhang J, et al. Warburg effect revisited: an epigenetic link between glycolysis and gastric carcinogenesis. Oncogene. 2010; 29(3): 442-450. doi: 10.1038/onc.2009.332

Kwon OH, Kang TW, Kim JH, et al. Pyruvate kinase M2 promotes the growth of gastric cancer cells via regulation of Bcl-xL expression at transcriptional level. Biochemical and bio-physical research communications. 2012; 423(1): 38-44. doi: 10.1016/j.bbrc.2012.05.063

Zhou CF, Li XB, Sun H, et al. Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells. IUBMB life. 2012; 64(9): 775- 782. doi: 10.1002/iub.1066

Hur H, Xuan Y, Kim YB, et al. Expression of pyruvate de-hydrogenase kinase-1 in gastric cancer as a potential therapeutic target. International journal of oncology. 2013; 42(1): 44-54. doi: 10.3892/ijo.2012.1687

Giatromanolaki A, Sivridis E, Maltezos E, et al. Hypoxia inducible factor 1alpha and 2alpha overexpression in inflamma-tory bowel disease. Journal of clinical pathology. 2003; 56(3): 209-213. doi: 10.1136/jcp.56.3.209

Vermeulen N, Vermeire S, Arijs I, et al. Seroreactivity against glycolytic enzymes in inflammatory bowel disease. In-flammatory bowel diseases. 2011; 17(2): 557-564. doi: 10.1002/ ibd.21388

Bobarykina AY, Minchenko DO, Opentanova IL, et al. Hy-poxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers. Acta biochimica Polonica. 2006; 53(4): 789-799.

Tong M, McHardy I, Ruegger P, et al. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. The ISME journal. 2014; 8(11): 2193-2206. doi: 10.1038/ismej.2014.64

Engelman JA, Chen L, Tan X, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nature medicine. 2008; 14(12): 1351-1356. doi: 10.1038/nm.1890

Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Dia-betes Care. 2009; 32(9): 1620-1625. doi: 10.2337/dc08-2175

Hawley SA, Fullerton MD, Ross FA, et al. The ancient drug salicylate directly activates AMP-activated protein kinase. Sci-ence. 2012; 336(6083): 918-922. doi: 10.1126/science.1215327

Beckers A, Organe S, Timmermans L, et al. Methotrex-ate enhances the antianabolic and antiproliferative effects of 5-aminoimidazole-4-carboxamide riboside. Molecular cancer therapeutics. 2006; 5(9): 2211-2217. doi: 10.1158/1535-7163. MCT-06-0001

Xuan Y, Hur H, Ham IH, et al. Dichloroacetate attenu-ates hypoxia-induced resistance to 5-fluorouracil in gastric cancer through the regulation of glucose metabolism. Experi-mental cell research. 2014; 321(2): 219-230. doi: 10.1016/j. yexcr.2013.12.009

Maschek G, Savaraj N, Priebe W, et al. 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. Cancer research. 2004; 64(1): 31-34. doi: 10.1158/0008-5472.CAN-03- 3294

Singh D, Banerji AK, Dwarakanath BS, et al. Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation stud-ies in patients with glioblastoma multiforme. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft [et al]. 2005; 181(8): 507-514. doi: 10.1007/s00066-005-1320-z

Nelson JA, Falk RE. Phloridzin and phloretin inhibition of 2-deoxy-D-glucose uptake by tumor cells in vitro and in vivo. Anticancer research. 1993; 13(6A): 2293-2299.

Nelson JA, Falk RE. The efficacy of phloridzin and phlo-retin on tumor cell growth. Anticancer research. 1993; 13(6A): 2287-2292.

Clem B, Telang S, Clem A, et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Molecular cancer therapeutics. 2008; 7(1): 110-120. doi: 10.1158/1535-7163.MCT-07-0482

Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: Two case reports. J Am Coll Nutr. 1995; 14(2): 202-208. doi: 10.1080/07315724.1995.10718495

Liu AM, Xu Z, Shek FH, et al. miR-122 targets pyru-vate kinase M2 and affects metabolism of hepatocellular car-cinoma. PLoS One. 2014; 9(1): e86872. doi: 10.1371/journal. pone.0086872

Published

2015-04-13

How to Cite

James J. Phelan, C. O’Hanlon, John V. Reynolds, & Jacintha O’Sullivan. (2015). The Role of Energy Metabolism in Driving Disease Progression in Inflammatory, Hypoxic and Angiogenic Microenvironments. Gastro, 1(2), 44–58. https://doi.org/10.17140/GOJ-1-108

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