Peroxisome proliferator-activated receptor-g activation inhibits tumor metastasis by antagonizing smad3-mediated epithelial-mesenchymal transition

Molecular Cancer Therapeutics

Volumn 9, Issue 12, 2010, Pages 3221-3232

  Reka, Ajaya Kumar ^a   Kurapati, Himabindu ^a   Narala, Venkata R ^a   Bommer, Guido ^b   Chen, Jun ^a   Standiford, Theodore J ^c   Keshamouni, Venkateshwar G ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b DE DUVE INSTITUTE   (Belgium)

^c YOGI VEMANA UNIVERSITY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; FIBRONECTIN; MATRIX METALLOPROTEINASE; NERVE CELL ADHESION MOLECULE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; ROSIGLITAZONE; SMAD2 PROTEIN; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TROGLITAZONE; UVOMORULIN; VIMENTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CANCER INVASION; CELL MIGRATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; GENE ACTIVATION; GENE REPRESSION; HUMAN; HUMAN TISSUE; LIGAND BINDING; LUNG CANCER; METASTASIS INHIBITION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; RECEPTOR GENE; TRANSACTIVATION;

ANIMALS; CADHERINS; CELL LINE, TUMOR; CELL MOVEMENT; CELL NUCLEUS; EPITHELIAL-MESENCHYMAL TRANSITION; GENE KNOCKDOWN TECHNIQUES; HUMANS; LIGANDS; LUNG NEOPLASMS; MICE; NEOPLASM METASTASIS; PHENOTYPE; PHOSPHORYLATION; PPAR GAMMA; PROMOTER REGIONS, GENETIC; PROTEIN TRANSPORT; SMAD2 PROTEIN; SMAD3 PROTEIN; TRANSCRIPTION, GENETIC; TRANSFORMING GROWTH FACTOR BETA; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 78650450648     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-10-0570     Document Type: Article

References (46)

1. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 2003;15(6):740-6.
2. Thiery JP, Sleeman JP. Complex networks orchestrate epithelialmesenchymal transitions. Nat Rev Mol Cell Biol 2006;7(2):131-42.
3. Tarin D, Thompson EW, Newgreen DF. The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res 2005;65 (14):5996-6000; discussion 1.
4. Zavadil J, Haley J, Kalluri R, Muthuswamy SK, Thompson E. Epithelialmesenchymal transition. Cancer Res 2008;68(23):9574-7.
5. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133(4):704-15.
6. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005;24(37):5764-74.
7. Elliott RL, Blobe GC. Role of transforming growth factor beta in human cancer. J Clin Oncol 2005;23(9):2078-93.
8. Kim WS, Park C, Jung YS, Kim HS, Han J, Park CH, et al. Reduced transforming growth factor-beta type II receptor (TGF-beta RII) expression in adenocarcinoma of the lung. Anticancer Res 1999;19 (1A):301-6.
9. Kong F, Jirtle RL, Huang DH, Clough RW, Anscher MS. Plasma transforming growth factor-beta1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma. Cancer 1999;86(9):1712-9.
10. Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, et al. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest 2002;109(12):1551-9.
11. Bates RC, Mercurio AM. The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther 2005;4(4):365-70.
12. Lemberger T, Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: A nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 1996;12:335-63.
13. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998;391(6662):79-82.
14. Fajas L, Debril MB, Auwerx J. Peroxisome proliferator-activated receptor-gamma: From adipogenesis to carcinogenesis. J Mol Endocrinol 2001;27(1):1-9.
15. Grommes C, Landreth GE, Heneka MT. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol 2004;5(7):419-29.
16. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-35.
17. Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, et al. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 1998;95(15):8806-11.
18. Kubota T, Koshizuka K, Williamson EA, Asou H, Said JW, Holden S, et al. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res 1998;58(15):3344-52.
19. Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med 1998;4(9 ):1046-52.
20. Keshamouni VG, Reddy RC, Arenberg DA, Joel B, Thannickal VJ, Kalemkerian GP, et al. Peroxisome proliferator-activated receptorgamma activation inhibits tumor progression in non-small-cell lung cancer. Oncogene 2004;23(1):100-8.
21. Reddy RC, SrirangamA, Reddy K, Chen J, Gangireddy S, Kalemkerian GP, et al. Chemotherapeutic drugs induce PPAR-gamma expression and show sequence-specific synergy with PPAR-gamma ligands in inhibition of non-small cell lung cancer. Neoplasia 2008;10(6):597-603.
22. Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. Differential protein expression profiling by iTRAQ- 2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res 2006;5(5):1143-54.
23. Yoshida D, Teramoto A. Elevated cell invasion is induced by hypoxia in a human pituitary adenoma cell line. Cell Adh Migr 2007;1(1):43-51.
24. Li Y, Lazar MA. Differential gene regulation by PPARgamma agonist and constitutively active PPARgamma2. Mol Endocrinol 2002;16 (5):1040-8.
25. Fu M, Zhang J, Zhu X, Myles DE, Willson TM, Liu X, et al. Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3. J Biol Chem 2001;276(49):45888-94.
26. Han C, Demetris AJ, Liu Y, Shelhamer JH, Wu T. Transforming growth factor-beta (TGF-beta) activates cytosolic phospholipase A2alpha (cPLA2alpha)-mediated prostaglandin E2 (PGE)2/EP1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)/Smad signaling pathways in human liver cancer cells. A novel mechanism for subversion of TGF-beta-induced mitoinhibition. J Biol Chem 2004;279(43):44344-54.
27. Ghosh AK, Bhattacharyya S, Wei J, Kim S, Barak Y, Mori Y, et al. Peroxisome proliferator-activated receptor-gamma abrogates Smaddependent collagen stimulation by targeting the p300 transcriptional coactivator. FASEB J 2009;23(9):2968-77.
28. Yao HW, Xie QM, Chen JQ, Deng YM, Tang HF. TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro. Life Sci 2004;76 (1):29-37.
29. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2(6):442-54.
30. Govindarajan R, Ratnasinghe L, Simmons DL, Siegel ER, Midathada MV, Kim L, et al. Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 2007;25(12):1476-81.
31. Tan X, Dagher H, Hutton CA, Bourke JE. Effects of PPAR gamma ligands on TGF-beta1-induced epithelial-mesenchymal transition in alveolar epithelial cells. Respir Res 2010 ;11:21.
32. Nemenoff RA. Peroxisome proliferator-activated receptor-gamma in lung cancer: Defining specific versus "off-target" effectors. J Thorac Oncol 2007;2(11):989-92.
33. Han S, Roman J. Rosiglitazone suppresses human lung carcinoma cell growth through PPARgamma-dependent and PPARgamma-independent signal pathways. Mol Cancer Ther 2006;5(2):430-7.
34. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 2008;68(10):3645-54.
35. Davies M, Robinson M, Smith E, Huntley S, Prime S, Paterson I. Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem 2005;95(5):918-31.
36. Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 2005;16(4):1987-2002.
37. Hoot KE, Lighthall J, Han G, Lu SL, Li A, Ju W, et al. Keratinocytespecific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest 2008;118(8):2722-32.
38. Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Kucherlapati R, et al. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Mol Cell Biol 2006;26(2):654-67.
39. Burstein HJ, Demetri GD, Mueller E, Sarraf P, Spiegelman BM, Winer EP. Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: A phase II study. Breast Cancer Res Treat 2003;79(3):391-7.
40. Yee LD, Williams N, Wen P, Young DC, Lester J, Johnson MV, et al. Pilot study of rosiglitazone therapy in women with breast cancer: Effects of short-term therapy on tumor tissue and serum markers. Clin Cancer Res 2007;13(1):246-52.
41. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, et al. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A 1999;96(7):3951-6.
42. Girnun GD, Chen L, Silvaggi J, Drapkin R, Chirieac LR, Padera RF, et al. Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin Cancer Res 2008;14 (20):6478-86.
43. Shimizu M, Moriwaki H. Synergistic effects of PPARgamma ligands and retinoids in cancer treatment. PPAR Res 2008;2008:181047.
44. Yang AD, Fan F, Camp ER, van Buren G, Liu W, Somcio R, et al. Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 2006;12 (14 Pt 1):4147-53.
45. Kajiyama H, Shibata K, Terauchi M, Yamashita M, Ino K, Nawa A, et al. Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol 2007;31(2):277-83.
46. Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 2005;65 (20):9455-62.