Molecular cross-regulation between PPAR-γ and other signaling pathways: Implications for lung cancer therapy

Lung Cancer

Volumn 72, Issue 2, 2011, Pages 154-159

  Reka, Ajaya Kumar ^a   Goswami, Moloy T ^a   Krishnapuram, Rashmi ^b   Standiford, Theodore J ^a   Keshamouni, Venkateshwar G ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

Author keywords

Lung cancer; PPAR ligands; Synergistic drug interactions; TGF ; Tumor microenvironment; TZDs

Indexed keywords

CIGLITAZONE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; ROSIGLITAZONE; TROGLITAZONE;

ADIPOCYTE; ANGIOGENESIS; APOPTOSIS; CELL DIFFERENTIATION; CELL PROLIFERATION; DRUG MECHANISM; HUMAN; INFLAMMATION; LIPID METABOLISM; LUNG CANCER; MACROPHAGE; METASTASIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; DRUG THERAPY; HUMANS; INFLAMMATION; LUNG NEOPLASMS; NEOPLASM METASTASIS; PPAR GAMMA; RECEPTOR CROSS-TALK; SIGNAL TRANSDUCTION;

EID: 79953774672     PISSN: 01695002     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.lungcan.2011.01.019     Document Type: Review

References (92)

1. Greenlee R.T., Murray T., Bolden S., Wingo P.A. Cancer statistics, 2000. CA Cancer J Clin 2000, 50:7-33.
2. Keshamouni V.G., Reddy R.C., Arenberg D.A., Joel B., Thannickal V.J., Kalemkerian G.P., et al. Peroxisome proliferator-activated receptor-γ activation inhibits tumor progression in non-small-cell lung cancer. Oncogene 2004, 23:100-108.
3. Li M., Lee T.W., Mok T.S., Warner T.D., Yim A.P., Chen G.G. Activation of peroxisome proliferator-activated receptor-γ by troglitazone (TGZ) inhibits human lung cell growth. J Cell Biochem 2005, 96:760-774.
4. Chang T.H., Szabo E. Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor γ in non-small cell lung cancer. Cancer Res 2000, 60:1129-1138.
5. Inoue K., Kawahito Y., Tsubouchi Y., Yamada R., Kohno M., Hosokawa Y., et al. Expression of peroxisome proliferator-activated receptor (PPAR)-γ in human lung cancer. Anticancer Res 2001, 21:2471-2476.
6. Mangelsdorf D.J., Thummel C., Beato M., Herrlich P., Schutz G., Umesono K., et al. The nuclear receptor superfamily: the second decade. Cell 1995, 83:835-839.
7. Zieleniak A., Wojcik M., Wozniak L.A. Structure and physiological functions of the human peroxisome proliferator-activated receptor γ. Arch Immunol Ther Exp (Warsz) 2008, 56:331-345.
8. Fajas L., Auboeuf D., Raspe E., Schoonjans K., Lefebvre A.M., Saladin R., et al. The organization, promoter analysis, and expression of the human PPARγ gene. J Biol Chem 1997, 272:18779-18789.
9. Issemann I., Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990, 347:645-650.
10. Misra P., Owuor E.D., Li W., Yu S., Qi C., Meyer K., et al. Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase. J Biol Chem 2002, 277:48745-48754.
11. Spiegelman B.M. PPAR-γ: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998, 47:507-514.
12. Tontonoz P., Hu E., Spiegelman B.M. Stimulation of adipogenesis in fibroblasts by PPAR γ 2, a lipid-activated transcription factor. Cell 1994, 79:1147-1156.
13. Lambe K.G., Tugwood J.D. A human peroxisome-proliferator-activated receptor-γ is activated by inducers of adipogenesis, including thiazolidinedione drugs. Eur J Biochem 1996, 239:1-7.
14. Werman A., Hollenberg A., Solanes G., Bjorbaek C., Vidal-Puig A.J., Flier J.S. Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor γ (PPARγ). Differential activity of PPARγ1 and -2 isoforms and influence of insulin. J Biol Chem 1997, 272:20230-20235.
15. Forman B.M., Tontonoz P., Chen J., Brun R.P., Spiegelman B.M., Evans R.M. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR γ. Cell 1995, 83:803-812.
16. Willson T.M., Brown P.J., Sternbach D.D., Henke B.R. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000, 43:527-550.
17. Kletzien R.F., Clarke S.D., Ulrich R.G. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol 1992, 41:393-398.
18. Shibata T., Matsui K., Nagao K., Shinkai H., Yonemori F., Wakitani K. Pharmacological profiles of a novel oral antidiabetic agent. JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol 1999, 364:211-219.
19. Suh N., Wang Y., Williams C.R., Risingsong R., Gilmer T., Willson T.M., et al. A new ligand for the peroxisome proliferator-activated receptor-γ (PPAR-γ), GW7845, inhibits rat mammary carcinogenesis. Cancer Res 1999, 59:5671-5673.
20. Hwang B.Y., Lee J.H., Nam J.B., Kim H.S., Hong Y.S., Lee J.J. Two new furanoditerpenes from Saururus chinenesis and their effects on the activation of peroxisome proliferator-activated receptor γ. J Nat Prod 2002, 65:616-617.
21. Kuroda M., Mimaki Y., Sashida Y., Mae T., Kishida H., Nishiyama T., et al. Phenolics with PPAR-γ ligand-binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice. Bioorg Med Chem Lett 2003, 13:4267-4272.
22. Xu J., Fu Y., Chen A. Activation of peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol 2003, 285:G20-30.
23. Desvergne B., Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999, 20:649-688.
24. IJpenberg A., Jeannin E., Wahli W., Desvergne B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J Biol Chem 1997, 272:20108-20117.
25. Kliewer S.A., Umesono K., Noonan D.J., Heyman R.A., Evans R.M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 1992, 358:771-774.
26. Daynes R.A., Jones D.C. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2002, 2:748-759.
27. Rochette-Egly C. Nuclear receptors: integration of multiple signalling pathways through phosphorylation. Cell Signal 2003, 15:355-366.
28. Standiford T.J., Keshamouni V.G., Reddy R.C. Peroxisome proliferator-activated receptor-{γ} as a regulator of lung inflammation and repair. Proc Am Thorac Soc 2005, 2:226-231.
29. Jiang C., Ting A.T., Seed B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 1998, 391:82-86.
30. Pascual G., Fong A.L., Ogawa S., Gamliel A., Li A.C., Perissi V., et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature 2005, 437:759-763.
31. Hu E., Kim J.B., Sarraf P., Spiegelman B.M. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARγ. Science 1996, 274:2100-2103.
32. Camp H.S., Tafuri S.R. Regulation of peroxisome proliferator-activated receptor γ activity by mitogen-activated protein kinase. J Biol Chem 1997, 272:10811-10816.
33. Adams M., Reginato M.J., Shao D., Lazar M.A., Chatterjee V.K. Transcriptional activation by peroxisome proliferator-activated receptor γ is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 1997, 272:5128-5132.
34. Burgermeister E., Seger R. PPARγ and MEK interactions in cancer. PPAR Res 2008, 2008:309469.
35. Burgermeister E., Seger R. MAPK kinases as nucleo-cytoplasmic shuttles for PPARγ. Cell Cycle 2007, 6:1539-1548.
36. Burgermeister E., Chuderland D., Hanoch T., Meyer M., Liscovitch M., Seger R. Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor γ. Mol Cell Biol 2007, 27:803-817.
37. Shao D., Rangwala S.M., Bailey S.T., Krakow S.L., Reginato M.J., Lazar M.A. Interdomain communication regulating ligand binding by PPAR-γ. Nature 1998, 396:377-380.
38. Prusty D., Park B.H., Davis K.E., Farmer S.R. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem 2002, 277:46226-46232.
39. Chuang C.C., Yang R.S., Tsai K.S., Ho F.M., Liu S.H. Hyperglycemia enhances adipogenic induction of lipid accumulation: involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor γ signaling. Endocrinology 2007, 148:4267-4275.
40. Hosooka T., Noguchi T., Kotani K., Nakamura T., Sakaue H., Inoue H., et al. Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-γ phosphorylation. Nat Med 2008, 14:188-193.
41. Coll T., Jove M., Rodriguez-Calvo R., Eyre E., Palomer X., Sanchez R.M., et al. Palmitate-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator 1α in skeletal muscle cells involves MEK1/2 and nuclear factor-κB activation. Diabetes 2006, 55:2779-2787.
42. Cagnol S., Chambard J.C. ERK and cell death: mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J 2010, 277:2-21.
43. Kim J., Adam R.M., Freeman M.R. Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation. Cancer Res 2002, 62:1549-1554.
44. Ricote M., Li A.C., Willson T.M., Kelly C.J., Glass C.K. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 1998, 391:79-82.
45. Hinz B., Brune K., Pahl A. 15-Deoxy-Delta(12,14)-prostaglandin J2 inhibits the expression of proinflammatory genes in human blood monocytes via a PPAR-γ-independent mechanism. Biochem Biophys Res Commun 2003, 302:415-420.
46. Chinetti G., Fruchart J.C., Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000, 49:497-505.
47. Shu H., Wong B., Zhou G., Li Y., Berger J., Woods J.W., et al. Activation of PPARα or γ reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commun 2000, 267:345-349.
48. Straus D.S., Glass C.K. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol 2007, 28:551-558.
49. Chen F., Wang M., O'Connor J.P., He M., Tripathi T., Harrison L.E. Phosphorylation of PPARγ via active ERK1/2 leads to its physical association with p65 and inhibition of NF-κβ. J Cell Biochem 2003, 90:732-744.
50. Castrillo A., Diaz-Guerra M.J., Hortelano S., Martin-Sanz P., Bosca L. Inhibition of IκB kinase and IκB phosphorylation by 15-deoxy-Delta(12,14)-prostaglandin J(2) in activated murine macrophages. Mol Cell Biol 2000, 20:1692-1698.
51. Straus D.S., Pascual G., Li M., Welch J.S., Ricote M., Hsiang C.H., et al. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-κ B signaling pathway. Proc Natl Acad Sci USA 2000, 97:4844-4849.
52. Chung S.W., Kang B.Y., Kim S.H., Pak Y.K., Cho D., Trinchieri G., et al. Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-γ and nuclear factor-κ B. J Biol Chem 2000, 275:32681-32687.
53. Bonofiglio D., Aquila S., Catalano S., Gabriele S., Belmonte M., Middea E., et al. Peroxisome proliferator-activated receptor-γ activates p53 gene promoter binding to the nuclear factor-κB sequence in human MCF7 breast cancer cells. Mol Endocrinol 2006, 20:3083-3092.
54. Vanden Berghe W., Vermeulen L., Delerive P., De Bosscher K., Staels B., Haegeman G. A paradigm for gene regulation: inflammation, NF-κB and PPAR. Adv Exp Med Biol 2003, 544:181-196.
55. Boyault S., Bianchi A., Moulin D., Morin S., Francois M., Netter P., et al. 15-Deoxy-delta(12,14)-prostaglandin J(2) inhibits IL-1β-induced IKK enzymatic activity and IκBα degradation in rat chondrocytes through a PPARγ-independent pathway. FEBS Lett 2004, 572:33-40.
56. Rossi A., Kapahi P., Natoli G., Takahashi T., Chen Y., Karin M., et al. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 2000, 403:103-108.
57. Delerive P., Gervois P., Fruchart J.C., Staels B. Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-α activators. J Biol Chem 2000, 275:36703-36707.
58. Ricote M., Glass C.K. PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta 2007, 1771:926-935.
59. Li M., Pascual G., Glass C.K. Peroxisome proliferator-activated receptor γ-dependent repression of the inducible nitric oxide synthase gene. Mol Cell Biol 2000, 20:4699-4707.
60. Attisano L., Wrana J.L. Signal transduction by the TGF-β superfamily. Science 2002, 296:1646-1647.
61. Nakao A., Imamura T., Souchelnytskyi S., Kawabata M., Ishisaki A., Oeda E., et al. TGF-β receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J 1997, 16:5353-5362.
62. Massague J. TGFβ in Cancer. Cell 2008, 134:215-230.
63. Reka A.K., Kurapati H., Narala V.R., Bommer G., Chen J., Standiford T.J., et al. Peroxisome proliferator-activated receptor-γ activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesencymal transition. Mol Cancer Ther 2010, 9(12):1-12.
64. Han C., Demetris A.J., Liu Y., Shelhamer J.H., Wu T. Transforming growth factor-β (TGF-β) activates cytosolic phospholipase A2α (cPLA2α)-mediated prostaglandin E2 (PGE)2/EP1 and peroxisome proliferator-activated receptor-γ (PPAR-γ)/Smad signaling pathways in human liver cancer cells. A novel mechanism for subversion of TGF-β-induced mitoinhibition. J Biol Chem 2004, 279:44344-44354.
65. Choy L., Derynck R. Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem 2003, 278:9609-9619.
66. Chou Y.T., Wang H., Chen Y., Danielpour D., Yang Y.C. Cited2 modulates TGF-β-mediated upregulation of MMP9. Oncogene 2006, 25:5547-5560.
67. Tien E.S., Davis J.W., Vanden Heuvel J.P. Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor α coregulator. J Biol Chem 2004, 279:24053-24063.
68. Redondo S., Ruiz E., Santos-Gallego C.G., Padilla E., Tejerina T. Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-γ, transforming growth factor-β1, and a Smad2-dependent mechanism. Diabetes 2005, 54:811-817.
69. Kalluri R., Weinberg R.A. The basics of epithelial-mesenchymal transition. J Clin Invest 2009, 119:1420-1428.
70. Shimoda M., Mellody K.T., Orimo A. Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol 2010, 21:19-25.
71. Burgess H.A., Daugherty L.E., Thatcher T.H., Lakatos H.F., Ray D.M., Redonnet M., et al. PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 2005, 288:L1146-1153.
72. Maeda A., Horikoshi S., Gohda T., Tsuge T., Maeda K., Tomino Y. Pioglitazone attenuates TGF-β(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)γ. Cell Biol Int 2005, 29:422-428.
73. Moustakas A., Heldin C.H. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 2007, 98:1512-1520.
74. Chang T.H., Szabo E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-γ and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res 2002, 8:1206-1212.
75. Han S., Sidell N., Fisher P.B., Roman J. Up-regulation of p21 gene expression by peroxisome proliferator-activated receptor γ in human lung carcinoma cells. Clin Cancer Res 2004, 10:1911-1919.
76. Satoh T., Toyoda M., Hoshino H., Monden T., Yamada M., Shimizu H., et al. Activation of peroxisome proliferator-activated receptor-γ stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells. Oncogene 2002, 21:2171-2180.
77. Han S., Roman J. Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways. Mol Cancer Ther 2006, 5:430-437.
78. Han S., Roman J. Suppression of prostaglandin E2 receptor subtype EP2 by PPARγ ligands inhibits human lung carcinoma cell growth. Biochem Biophys Res Commun 2004, 314:1093-1099.
79. Hazra S., Batra R.K., Tai H.H., Sharma S., Cui X., Dubinett S.M. Pioglitazone and rosiglitazone decrease prostaglandin E2 in non-small-cell lung cancer cells by up-regulating 15-hydroxyprostaglandin dehydrogenase. Mol Pharmacol 2007, 71:1715-1720.
80. Winn R.A., Van Scoyk M., Hammond M., Rodriguez K., Crossno J.T., Heasley L.E., et al. Antitumorigenic effect of Wnt 7a and Fzd 9 in non-small cell lung cancer cells is mediated through ERK-5-dependent activation of peroxisome proliferator-activated receptor γ. J Biol Chem 2006, 281:26943-26950.
81. Bren-Mattison Y., Van Putten V., Chan D., Winn R., Geraci M.W., Nemenoff R.A. Peroxisome proliferator-activated receptor-γ (PPAR(γ)) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC). Oncogene 2005, 24:1412-1422.
82. Panigrahy D., Singer S., Shen L.Q., Butterfield C.E., Freedman D.A., Chen E.J., et al. PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 2002, 110:923-932.
83. Keshamouni V.G., Arenberg D.A., Reddy R.C., Newstead M.J., Anthwal S., Standiford T.J. PPAR-γ activation inhibits angiogenesis by blocking ELR+CXC chemokine production in non-small cell lung cancer. Neoplasia 2005, 7:294-301.
84. Han S., Ritzenthaler J.D., Rivera H.N., Roman J. Peroxisome proliferator-activated receptor-γ ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1. Am J Physiol Lung Cell Mol Physiol 2005, 289:L419-428.
85. Han S., Rivera H.N., Roman J. Peroxisome proliferator-activated receptor-γ ligands inhibit α5 integrin gene transcription in non-small cell lung carcinoma cells. Am J Respir Cell Mol Biol 2005, 32:350-359.
86. Van Ginderachter J.A., Meerschaut S., Liu Y., Brys L., De Groeve K., Hassanzadeh Ghassabeh G., et al. Peroxisome proliferator-activated receptor γ (PPARγ) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer. Blood 2006, 108:525-535.
87. Girnun G.D., Chen L., Silvaggi J., Drapkin R., Chirieac L.R., Padera R.F., et al. Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin Cancer Res 2008, 14:6478-6486.
88. Girnun G.D., Naseri E., Vafai S.B., Qu L., Szwaya J.D., Bronson R., et al. Synergy between PPARγ ligands and platinum-based drugs in cancer. Cancer Cell 2007, 11:395-406.
89. Reddy R.C., Srirangam A., Reddy K., Chen J., Gangireddy S., Kalemkerian G.P., et al. Chemotherapeutic drugs induce PPAR-γ expression and show sequence-specific synergy with PPAR-γ ligands in inhibition of non-small cell lung cancer. Neoplasia 2008, 10:597-603.
90. Lee S.Y., Hur G.Y., Jung K.H., Jung H.C., Kim J.H., Shin C., et al. PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression. Lung Cancer 2006, 51:297-301.
91. Yao C.J., Lai G.M., Chan C.F., Cheng A.L., Yang Y.Y., Chuang S.E. Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone. Int J Cancer 2006, 118:773-779.
92. Govindarajan R., Ratnasinghe L., Simmons D.L., Siegel E.R., Midathada M.V., Kim L., et al. Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 2007, 25:1476-1481.