Peroxisome Proliferator-Activated Receptor Gamma and regulations by the ubiquitin-proteasome system in pancreatic cancer

PPAR Research

Volumn , Issue , 2012, Pages

  Stravodimou, Athina ^a   Mazzoccoli, Gianluigi ^b   Voutsadakis, Ioannis A ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 5 NITRO N (4 PYRIDYL)BENZAMIDE; CIGLITAZONE; CYCLIN D1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEASOME; PROTEIN CDC42; PROTEIN KINASE C; RAC1 PROTEIN; ROSIGLITAZONE; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TROGLITAZONE; UBIQUITIN;

ADIPOCYTE; CARCINOGENESIS; CELL ADHESION; CELL CYCLE ARREST; CELL PROLIFERATION; CYSTIC FIBROSIS; DISEASE ASSOCIATION; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION; HUMAN; MICROENVIRONMENT; NONHUMAN; OBESITY; PANCREAS CANCER; PANCREATIC STELLATE CELL; PANCREATITIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; SUMOYLATION; UBIQUITINATION;

EID: 84867369739     PISSN: 16874757     EISSN: 16874765     Source Type: Journal    
DOI: 10.1155/2012/367450     Document Type: Review

References (125)

1. Manuel H., Pancreatic cancer. The New England Journal of Medicine 2010 362 17 1605 1617 2-s2.0-77951755278 10.1056/NEJMra0901557
2. Burris H. A. III, Moore M. J., Andersen J., Green M. R., Rothenberg M. L., Modiano M. R., Cripps M. C., Portenoy R. K., Storniolo A. M., Tarassoff P., Nelson R., Dorr F. A., Stephens C. D., Von Hoff D. D., Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Journal of Clinical Oncology 1997 15 6 2403 2413 2-s2.0-8244254377 (Pubitemid 27251144)
3. Conroy T., Desseigne F., Ychou M., Bouché O., Guimbaud R., Bécouarn Y., Adenis A., Raoul J. L., Gourgou-Bourgade S., De La Fouchardière C., Bennouna J., Bachet J. B., Khemissa-Akouz F., Péré-Vergé D., Delbaldo C., Assenat E., Chauffert B., Michel P., Montoto-Grillot C., Ducreux M., FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. The New England Journal of Medicine 2011 364 19 1817 1825 2-s2.0-79955921754 10.1056/NEJMoa1011923
4. Voutsadakis I. A., Molecular predictors of gemcitabine response in pancreatic cancer. World Journal of Gastrointestinal Oncology 2011 3 11 153 164
5. Kristiansen G., Jacob J., Buckendahl A. C., Grützmann R., Alldinger I., Sipos B., Klöppel G., Bahra M., Langrehr J. M., Neuhaus P., Dietel M., Pilarsky C., Peroxisome proliferator-activated receptor γ is highly expressed in pancreatic cancer and is associated with shorter overall survival times. Clinical Cancer Research 2006 12 21 6444 6451 2-s2.0-33751303104 10.1158/1078-0432.CCR-06-0834 (Pubitemid 44799717)
6. Vigouroux C., Fajas L., Khallouf E., Meier M., Gyapay G., Lascols O., Auwerx J., Weissenbach J., Capeau J., Magré J., Human peroxisome proliferator-activated receptor- γ 2: genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsible for lipoatrophic diabetes. Diabetes 1998 47 3 490 492 2-s2.0-0031914386 10.2337/diabetes.47.3.490 (Pubitemid 28104216)
7. Fajas L., Auboeuf D., Raspé E., Schoonjans K., Lefebvre A. M., Saladin R., Najib J., Laville M., Fruchart J. C., Deeb S., Vidal-Puig A., Flier J., Briggs M. R., Staels B., Vidal H., Auwerx J., The organization, promoter analysis, and expression of the human PPAR γ gene. Journal of Biological Chemistry 1997 272 30 18779 18789 2-s2.0-0030835678 10.1074/jbc.272.30.18779 (Pubitemid 27318225)
8. Huin C., Corriveau L., Bianchi A., Keller J. M., Collet P., Krémarik-Bouillaud P., Domenjoud L., Bécuwe P., Schohn H., Ménard D., Daua M., Differential expression of peroxisome proliferator-activated receptors (PPARs) in the developing human fetal digestive tract. Journal of Histochemistry and Cytochemistry 2000 48 5 603 611 2-s2.0-17544387857 (Pubitemid 30233184)
9. Abbott B. D., Wood C. R., Watkins A. M., Das K. P., Lau C. S., Peroxisome proliferator-activated receptors alpha, beta, and gamma mRNA and protein expression in human fetal tissues. PPAR Research 2010 2010 19 2-s2.0-77956803359 10.1155/2010/690907 690907
10. Voutsadakis I. A., Peroxisome proliferator-activated receptor γ (PPAR γ) and colorectal carcinogenesis. Journal of Cancer Research and Clinical Oncology 2007 133 12 917 928 2-s2.0-35248869149 10.1007/s00432-007- 0277-y (Pubitemid 47561718)
11. Mandrup S., Bugge A., Molecular mechanisms and genome-wide aspects of PPAR subtype specific transactivation. PPAR Research 2010 2010 12 2-s2.0-77957933413 10.1155/2010/169506 169506
12. Yki-Järvinen H., Thiazolidinediones. The New England Journal of Medicine 2004 351 11 1106 1118 2-s2.0-19244365650 10.1056/NEJMra041001 (Pubitemid 39167514)
13. Diradourian C., Girard J., Pégorier J. P., Phosphorylation of PPARs: from molecular characterization to physiological relevance. Biochimie 2005 87 1 33 38 2-s2.0-14544272384 10.1016/j.biochi.2004.11.010 (Pubitemid 40298763)
14. Camp H. S., Tafuri S. R., Regulation of peroxisome proliferator-activated receptor γ activity by mitogen-activated protein kinase. Journal of Biological Chemistry 1997 272 16 10811 10816 2-s2.0-0030964085 10.1074/jbc.272.16.10811 (Pubitemid 27181096)
15. 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 6709 377 380 2-s2.0-0032569902 10.1038/24634 (Pubitemid 28557399)
16. Voutsadakis I. A., Ubiquitin, ubiquitination and the ubiquitin-proteasome system in cancer. Atlas of Genetics and Cytogenetics in Oncology and Haematology 2010 14 11 1088 1099
17. Schulman B. A., Harper J. W., Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nature Reviews Molecular Cell Biology 2009 10 5 319 331 2-s2.0-67349256160 10.1038/nrm2673
18. van Wijk S. J. L., Timmers H. T. M., The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins. The FASEB Journal 2010 24 4 981 993 2-s2.0-77951651753 10.1096/fj.09-136259
19. Metzger M. B., Hristova V. A., Weissman A. M., HECT and RING finger families of E3 ubiquitin ligases at a glance. Journal of Cell Science 2012 125 531 537
20. Li W., Ye Y., Polyubiquitin chains: functions, structures, and mechanisms. Cellular and Molecular Life Sciences 2008 65 15 2397 2406 2-s2.0-49249120530 10.1007/s00018-008-8090-6
21. Clague M. J., Coulson J. M., Urbé S., Cellular functions of the DUBs. Journal of Cell Science 2012 125 277 286
22. Walczak H., Iwai K., Dikic I., Generation and physiological roles of linear ubiquitin chains. BMC Biology 2012 10, article 23 6 10.1186/1741-7007-10- 23
23. Behrends C., Harper J. W., Constructing and decoding unconventional ubiquitin chains. Nature Structural and Molecular Biology 2011 18 5 520 528 2-s2.0-79955620198 10.1038/nsmb.2066
24. Voutsadakis I. A., Pathogenesis of colorectal carcinoma and therapeutic implications: the roles of the ubiquitin-proteasome system and Cox-2: cancer. Journal of Cellular and Molecular Medicine 2007 11 2 252 285 2-s2.0-34247887546 10.1111/j.1582-4934.2007.00032.x (Pubitemid 46695694)
25. Kravtsova-Ivantsiv Y., Ciechanover A., Non-canonical ubiquitin-based signals for proteasomal degradation. Journal of Cell Science 2012 125 539 548
26. Haglund K., Dikic I., The role of ubiquitylation in receptor endocytosis and endosomal sorting. Journal of Cell Science 2012 125 265 275
27. Bergink S., Jentsch S., Principles of ubiquitin and SUMO modifications in DNA repair. Nature 2009 458 7237 461 467 2-s2.0-63649144413 10.1038/nature07963
28. Mocciaro A., Rape M., Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control. Journal of Cell Science 2012 125 255 263
29. Ulrich H. D., Ubiquitin and SUMO in DNA repair at a glance. Journal of Cell Science 2012 125 249 254
30. Winget J. M., Mayor T., The diversity of ubiquitin recognition: hot spots and varied specificity. Molecular Cell 2010 38 5 627 635 2-s2.0-77953108542 10.1016/j.molcel.2010.05.003
31. Rechsteiner M., Mayer R. J., Ciechanover A., Rechsteiner M., The 26S proteasome. Protein Degradation 2005 1 New York, NY, USA Wiley-VCH 220 247
32. Wolf D. H., Hilt W., The proteasome: a proteolytic nanomachine of cell regulation and waste disposal. Biochimica et Biophysica Acta 2004 1695 13 19 31 2-s2.0-9644300915 10.1016/j.bbamcr.2004.10.007 (Pubitemid 39574965)
33. Harris J. L., Alper P. B., Li J., Rechsteiner M., Backes B. J., Substrate specificity of the human proteasome. Chemistry and Biology 2001 8 12 1131 1141 2-s2.0-0035542852 10.1016/S1074-5521(01)00080-1 (Pubitemid 34029882)
34. Nawaz Z., O'Malley B. W., Urban renewal in the nucleus: is protein turnover by proteasomes absolutely required for nuclear receptor-regulated transcription? Molecular Endocrinology 2004 18 3 493 499 2-s2.0-1542297619 10.1210/me.2003-0388 (Pubitemid 38328197)
35. Voutsadakis I. A., Papandreou C. N., The ubiquitin-proteasome system in prostate cancer and its transition to castration resistance. Urologic Oncology. In press
36. Perissi V., Aggarwal A., Glass C. K., Rose D. W., Rosenfeld M. G., A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell 2004 116 4 511 526 2-s2.0-1342264315 10.1016/S0092-8674(04)00133-3 (Pubitemid 38264429)
37. Hauser S., Adelmant G., Sarraf P., Wright H. M., Mueller E., Spiegelman B. M., Degradation of the peroxisome proliferator-activated receptor γ is linked to ligand-dependent activation. Journal of Biological Chemistry 2000 275 24 18527 18533 2-s2.0-0034674567 10.1074/jbc.M001297200 (Pubitemid 30414814)
38. Lefebvre B., Benomar Y., Guédin A., Langlois A., Hennuyer N., Dumont J., Bouchaert E., Dacquet C., Pénicaud L., Casteilla L., Pattou F., Ktorza A., Staels B., Lefebvre P., Proteasomal degradation of retinoid X receptor α reprograms transcriptional activity of PPAR γ in obese mice and humans. Journal of Clinical Investigation 2010 120 5 1454 1468 2-s2.0-77951865861 10.1172/JCI38606
39. Wei P., Pan D., Mao C., Wang Y.-X., RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1 α and Modulates brown fat cell metabolism. Molecular and Cellular Biology 2012 32 2 266 275 2-s2.0-84863067775 10.1128/MCB.05674-11
40. Amazit L., Roseau A., Khan J. A., Chauchereau A., Tyagi R. K., Loosfelt H., Leclerc P., Lombès M., Guiochon-Mantel A., Ligand-dependent degradation of SRC-1 is pivotal for progesterone receptor transcriptional activity. Molecular Endocrinology 2011 25 3 394 408 2-s2.0-79952181752 10.1210/me.2010-0458
41. Ferry C., Gaouar S., Fischer B., Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response. Journal of Biological Chemistry 2011 108 51 20603 20608
42. Wu R. C., Feng Q., Lonard D. M., O'Malley B. W., SRC-3 coactivator functional lifetime is regulated by a phosphor-dependent ubiquitin time clock. Cell 2007 129 6 1125 1140 2-s2.0-34250001084 10.1016/j.cell.2007.04.039 (Pubitemid 46891039)
43. Praefcke G. J. K., Hofmann K., Dohmen R. J., SUMO playing tag with ubiquitin. Trends in Biochemical Sciences 2012 37 1 23 31
44. Pascual G., Fong A. L., Ogawa S., Gamliel A., Li A. C., Perissi V., Rose D. W., Willson T. M., Rosenfeld M. G., Glass C. K., A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR- γ Nature 2005 437 7059 759 763 2-s2.0-26444471700 10.1038/nature03988 (Pubitemid 41486547)
45. Chung S. S., Ahn B. Y., Kim M., Choi H. H., Park H. S., Kang S., Park S. G., Kim Y. B., Cho Y. M., Lee H. K., Chung C. H., Park K. S., Control of adipogenesis by the SUMO-specific protease SENP2. Molecular and Cellular Biology 2010 30 9 2135 2146 2-s2.0-77950686220 10.1128/MCB.00852-09
46. Rytinki M. M., Palvimo J. J., SUMOylation attenuates the function of PGC-1 α Journal of Biological Chemistry 2009 284 38 26184 26193 2-s2.0-70350031566 10.1074/jbc.M109.038943
47. Anbalagan M., Huderson B., Murphy L., Rowan B. G., Post-translational modifications of nuclear receptors and human disease. Nuclear Receptor Signaling 2012 10 1 13
48. Luconi M., Cantini G., Serio M., Peroxisome proliferator-activated receptor gamma (PPAR γ): is the genomic activity the only answer? Steroids 2010 75 8-9 585 594 2-s2.0-77954244708 10.1016/j.steroids.2009.10.012
49. Toyota M., Miyazaki Y., Kitamura S., Nagasawa Y., Kiyohara T., Shinomura Y., Matsuzawa Y., Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1. Life Sciences 2002 70 13 1565 1575 2-s2.0-0037083972 10.1016/S0024-3205(01)01524-7 (Pubitemid 34164550)
50. Kawa S., Nikaido T., Unno H., Usuda N., Nakayama K., Kiyosawa K., Growth inhibition and differentiation of pancreatic cancer cell lines by PPAR γ ligand troglitazone. Pancreas 2002 24 1 1 7 2-s2.0-0036135985 10.1097/00006676-200201000-00001 (Pubitemid 34019653)
51. Hashimoto K., Farrow B. J., Evers B. M., Activation and role of MAP Kinases in 15d-PGJ2-induced apoptosis in the human pancreatic cancer cell line MIA PaCa-2. Pancreas 2004 28 2 153 159 2-s2.0-1442304433 10.1097/00006676- 200403000-00006 (Pubitemid 38269775)
52. Motomura W., Nagamine M., Tanno S., Sawamukai M., Takahashi N., Kohgo Y., Okumura T., Inhibition of cell invasion and morphological change by troglitazone in human pancreatic cancer cells. Journal of Gastroenterology 2004 39 5 461 468 2-s2.0-3042569217 10.1007/s00535-003-1324-3 (Pubitemid 38811730)
53. Sawai H., Liu J., Reber H. A., Hines O. J., Eibl G., Activation of peroxisome proliferator-activated receptor- γ decreases pancreatic cancer cell invasion through modulation of the plasminogen activator system. Molecular Cancer Research 2006 4 3 159 167 2-s2.0-33645717060 10.1158/1541-7786.MCR-05- 0257
54. Galli A., Ceni E., Crabb D. W., Mello T., Salzano R., Grappone C., Milani S., Surrenti E., Surrenti C., Casini A., Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPAR γ independent mechanisms. Gut 2004 53 11 1688 1697 2-s2.0-7244234089 10.1136/gut.2003.031997 (Pubitemid 39434116)
55. Ceni E., Mello T., Tarocchi M., Crabb D. W., Caldini A., Invernizzi P., Surrenti C., Milani S., Galli A., Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells. World Journal of Gastroenterology 2005 11 8 1122 1130 2-s2.0-14844350942 (Pubitemid 40352997)
56. Tsujie M., Nakamori S., Okami J., Hayashi N., Hiraoka N., Nagano H., Dono K., Umeshita K., Sakon M., Monden M., Thiazolidinediones inhibit growth of gastrointestinal, biliary, and pancreatic adenocarcinoma cells through activation of the peroxisome proliferator-activated receptor γ /retinoid X receptor α pathway. Experimental Cell Research 2003 289 1 143 151 2-s2.0-0043163884 10.1016/S0014-4827(03)00263-5 (Pubitemid 36993844)
57. Takeuchi Y., Takahashi M., Sakano K., Mutoh M., Niho N., Yamamoto M., Sato H., Sugimura T., Wakabayashi K., Suppression of N-nitrosobis(2-oxopropyl) amine-induced pancreatic carcinogenesis in hamsters by pioglitazone, a ligand of peroxisome proliferator-activated receptor γ Carcinogenesis 2007 28 8 1692 1696 2-s2.0-34548063105 10.1093/carcin/bgm095 (Pubitemid 47289030)
58. Dong Y. W., Wang X. P., Wu K., Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition. World Journal of Gastroenterology 2009 15 4 441 448 2-s2.0-59249086761 10.3748/wjg.15.441
59. Nakajima A., Tomimoto A., Fujita K., Sugiyama M., Takahashi H., Ikeda I., Hosono K., Endo H., Yoneda K., Iida H., Inamori M., Kubota K., Saito S., Nakajima N., Wada K., Nagashima Y., Nakagama H., Inhibition of peroxisome proliferator-activated receptor γ activity suppresses pancreatic cancer cell motility. Cancer Science 2008 99 10 1892 1900 2-s2.0-54949147269 10.1111/j.1349-7006.2008.00904.x
60. Abramson M. A., Jazag A., van der Zee J. A., Whang E. E., The molecular biology of pancreatic cancer. Gastrointestinal Cancer Research 2007 1 supplement 2 S7 S12
61. Cox A. D., Der C. J., Ras history: the saga continues. Small GTPases 2010 1 1 2 27 2-s2.0-78649474147 10.4161/sgtp.1.1.12178
62. Farrow B., Evers B. M., Activation of PPAR γ increases PTEN expression in pancreatic cancer cells. Biochemical and Biophysical Research Communications 2003 301 1 50 53 2-s2.0-0037473753 10.1016/S0006-291X(02)02983-2 (Pubitemid 36268846)
63. Patel L., Pass I., Coxon P., Downes C. P., Smith S. A., Macphee C. H., Tumor suppressor and anti-inflammatory actions of PPAR γ agonists are mediated via upregulation of PTEN. Current Biology 2001 11 10 764 768 2-s2.0-0035873953 10.1016/S0960-9822(01)00225-1 (Pubitemid 32442793)
64. Leslie N. R., Foti M., Non-genomic loss of PTEN function in cancer: not in my genes. Trends in Pharmacological Sciences 2011 32 3 131 140 2-s2.0-79952450963 10.1016/j.tips.2010.12.005
65. Schmukle A. C., Walczak H., No one can whistle a symphony alone- how different ubiquitin linkages cooperate to orchestrate NF- κ B activity. Journal of Cell Science 2012 125 549 559
66. Manenti S., Delmas C., Darbon J. M., Cell adhesion protects c-Raf-1 against ubiquitin-dependent degradation by the proteasome. Biochemical and Biophysical Research Communications 2002 294 5 976 980 2-s2.0-0036288581 10.1016/S0006-291X(02)00594-6 (Pubitemid 34687145)
67. Lu Z., Xu S., Joazeiro C., Cobb M. H., Hunter T., The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2. Molecular Cell 2002 9 5 945 956 2-s2.0-0036279167 10.1016/S1097-2765(02) 00519-1 (Pubitemid 34626666)
68. Coulombe P., Rodier G., Pelletier S., Pellerin J., Meloche S., Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation. Molecular and Cellular Biology 2003 23 13 4542 4558 2-s2.0-0038721214 10.1128/MCB.23.13.4542-4558.2003 (Pubitemid 36734745)
69. Guenou H., Kaabeche K., Dufour C., Miraoui H., Marie P. J., Down-regulation of ubiquitin ligase Cbl induced by twist haploinsufficiency in Saethre-Chotzen syndrome results in increased PI3K/Akt signaling and osteoblast proliferation. American Journal of Pathology 2006 169 4 1303 1311 2-s2.0-38849132555 10.2353/ajpath.2006.060102 (Pubitemid 351194365)
70. Adachi M., Katsumura K. R., Fujii K., Kobayashi S., Aoki H., Matsuzaki M., Proteasome-dependent decrease in Akt by growth factors in vascular smooth muscle cells. FEBS Letters 2003 554 1-2 77 80 2-s2.0-0142184484 10.1016/S0014-5793(03)01109-8 (Pubitemid 37324818)
71. Li J., Poi M. J., Tsai M. D., Regulatory mechanisms of tumor suppressor P16INK4A and their relevance to cancer. Biochemistry 2011 50 25 5566 5582 2-s2.0-79959412690 10.1021/bi200642e
72. Wang Z., Banerjee S., Ahmad A., Li Y., Azmi A. S., Gunn J. R., Kong D., Bao B., Ali S., Gao J., Mohammad R. M., Miele L., Korc M., Sarkar F. H., Activated K-ras and INK4a/Arf deficiency cooperate during the development of pancreatic cancer by activation of notch and NF- κ B signaling pathways. PLoS ONE 2011 6 6 2-s2.0-79958045469 10.1371/journal.pone.0020537 e20537
73. Barbash O., Egan E., Pontano L. L., Kosak J., Diehl J. A., Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF Fbx4/ α B-crystallin ligase and subsequent proteasome-dependent degradation. Oncogene 2009 28 49 4317 4325 2-s2.0-72049125085 10.1038/onc.2009.287
74. Fajas L., Egler V., Reiter R., Miard S., Lefebvre A. M., Auwerx J., PPAR γ controls cell proliferation and apoptosis in an RB-dependent manner. Oncogene 2003 22 27 4186 4193 2-s2.0-0037699445 10.1038/sj.onc.1206530 (Pubitemid 36876239)
75. Zand H., Rhimipour A., Bakhshayesh M., Shafiee M., Nour Mohammadi I., Salimi S., Involvement of PPAR- γ and p53 in DHA-induced apoptosis in Reh cells. Molecular and Cellular Biochemistry 2007 304 1-2 71 77 2-s2.0-34748848017 10.1007/s11010-007-9487-5 (Pubitemid 47484720)
76. Han C., Demetris A. J., Michalopoulos G. K., Zhan Q., Shelhamer J. H., Wu T., PPAR γ ligands inhibit cholangiocarcinoma cell growth through p53-dependent GADD45 and p21WAF1/Cip1 pathway. Hepatology 2003 38 1 167 177 2-s2.0-0038121972 10.1053/jhep.2003.50296 (Pubitemid 36775808)
77. Bonofiglio D., Cione E., Vizza D., Perri M., Pingitore A., Qi H., Catalano S., Rovito D., Genchi G., Andò S., Bid as a potential target of apoptotic effects exerted by low doses of PPAR γ and RXR ligands in breast cancer cells. Cell Cycle 2011 10 14 2344 2354 2-s2.0-79960453436 10.4161/cc.10.14.15917
78. Solomon H., Madar S., Rotter V., Mutant p53 gain of function is interwoven into the hallmarks of cancer. Journal of Pathology 2011 225 4 475 478
79. Blackford A., Serrano O. K., Wolfgang C. L., Parmigiani G., Jones S., Zhang X., Parsons D. W., Lin J. C. H., Leary R. J., Eshleman J. R., Goggins M., Jaffee E. M., Iacobuzio-Donahue C. A., Maitra A., Cameron J. L., Olino K., Schulick R., Winter J., Herman J. M., Laheru D., Klein A. P., Vogelstein B., Kinzler K. W., Velculescu V. E., Hruban R. H., SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clinical Cancer Research 2009 15 14 4674 4679 2-s2.0-68049115773 10.1158/1078-0432.CCR-09-0227
80. Massagué J., TGF β in cancer. Cell 2008 134 2 215 230 2-s2.0-47549090432 10.1016/j.cell.2008.07.001 (Pubitemid 352010335)
81. Gong K., Chen Y.-F., Li P., Transforming growth factor- β inhibits myocardial PPAR β expression in pressure overload-induced cardiac fibrosis and remodeling in mice. Journal of Hypertension 2011 29 9 1810 1819
82. Subramanian V., Golledge J., Heywood E. B., Bruemmer D., Daugherty A., Regulation of peroxisome proliferator-activated receptor- γ by angiotensin II via transforming growth factor- β 1-activated p38 mitogen-activated protein kinase in aortic smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology 2012 32 2 397 405
83. Kulkarni A. A., Thatcher T. H., Olsen K. C., Maggirwar S. B., Phipps R. P., Sime P. J., PPAR- γ ligands repress TGF β -induced myofibroblast differentiation by targeting the PI3K/Akt pathway: implications for therapy of fibrosis. PLoS ONE 2011 6 1 2-s2.0-79251563128 10.1371/journal.pone.0015909 e15909
84. Yu J. H., Kim K. H., Kim H., SOCS3 and PPAR- γ ligands inhibit the expression of IL-6 and TGF- β 1 by regulating JAK2/STAT3 signaling in pancreas. International Journal of Biochemistry and Cell Biology 2008 40 4 677 688 2-s2.0-39749117424 10.1016/j.biocel.2007.10.007 (Pubitemid 351297741)
85. Inoue Y., Imamura T., Regulation of TGF- β family signaling by E3 ubiquitin ligases. Cancer Science 2008 99 11 2107 2112 2-s2.0-55449107515 10.1111/j.1349-7006.2008.00925.x
86. Huang F., Chen Y.-G., Regulation of TGF- β receptor activity. Cell and Bioscience 2012 2 9 1 10
87. Polo S., Signaling-mediated control of ubiquitin ligases in endocytosis. BMC Biology 2012 10, article 25 9 10.1186/1741-7007-10-25
88. Tang L.-Y., Zhang Y. E., Non-degradative ubiquitination in Smad-dependent TGF- β signaling. Cell and Bioscience 2011 1 43 1 5
89. Morén A., Hellman U., Inada Y., Imamura T., Heldin C. H., Moustakas A., Differential ubiquitination defines the functional status of the tumor suppressor Smad4. Journal of Biological Chemistry 2003 278 35 33571 33582 2-s2.0-0042858169 10.1074/jbc.M300159200 (Pubitemid 37055811)
90. Bao B., Wang Z., Li Y., Kong D., Ali S., Banerjee S., Ahmad A., Sarkar F. H., The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochimica et Biophysica Acta 2011 1815 2 135 146 2-s2.0-78651355589 10.1016/j.bbcan.2010.11.003
91. Ben-Neriah Y., Karin M., Inflammation meets cancer, with NF- κ B as the matchmaker. Nature Immunology 2011 12 8 715 723
92. Maniati E., Bossard M., Cook N., Crosstalk between the canonical NF- κ B and Notch signaling pathways inhibits Ppar γ expression and promotes pancreatic cancer progression in mice. Journal of Clinical Investigation 2011 121 12 4685 4699
93. Voutsadakis I. A., Cho C. H., Yu J., Peroxisome Proliferator Activated Receptor- γ (PPAR γ): roles in chronic inflammation and intestinal oncogenic transformation. From Inflammation to Cancer. Advances in Diagnosis and Therapy for Gastrointestinal and Hepatological Diseases 2012 River Edge, NJ, USA World Scientific
94. Asano T., Yao Y., Zhu J., Li D., Abbruzzese J. L., Reddy S. A. G., The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF- κ B and c-Myc in pancreatic cancer cells. Oncogene 2004 23 53 8571 8580 2-s2.0-9644253003 10.1038/sj.onc.1207902 (Pubitemid 39576463)
95. Ying H., Elpek K. G., Vinjamoori A., PTEN is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF- κ B-cytokine network. Cancer Discovery 2011 1 2 158 169
96. 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 6662 79 82 2-s2.0-0031886864 10.1038/34178 (Pubitemid 28079218)
97. Jiang C., Ting A. T., Seed B., PPAR- γ agonists inhibit production of monocyte inflammatory cytokines. Nature 1998 391 6662 82 86 2-s2.0-0031888958 10.1038/34184 (Pubitemid 28079219)
98. Shields M. A., Dangi-Garimella S., Redig A. J., Munshi H. G., Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochemical Journal 2012 441 2 541 552
99. Chapnick D. A., Warner L., Bernet J., Rao T., Liu X., Partners in crime: the TGF β and MAPK pathways in cancer progression. Cell and Bioscience 2011 1 42 1 8
100. Lee S. J., Yang E. K., Kim S. G., Peroxisome proliferator-activated receptor- γ and retinoic acid X receptor α represses the TGF β 1 gene via PTEN-mediated p70 ribosomal S6 kinase-1 inhibition: role for Zf9 dephosphorylation. Molecular Pharmacology 2006 70 1 415 425
101. 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 Molecular and Cellular Biology 2007 27 3 803 817 2-s2.0-33846590071 10.1128/MCB.00601-06 (Pubitemid 46174547)
102. Jaster R., Molecular regulation of pancreatic stellate cell function. Molecular Cancer 2004 3, article 26 8 2-s2.0-13644267274 10.1186/1476-4598-3-26 (Pubitemid 40230546)
103. Apte M. V., Wilson J. S., Dangerous liaisons: pancreatic stellate cells and pancreatic cancer cells. Journal of Gastroenterology and Hepatology 2012 27 supplement 2 69 74
104. Bachem M. G., Schünemann M., Ramadani M., Siech M., Beger H., Buck A., Zhou S., Schmid-Kotsas A., Adler G., Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells. Gastroenterology 2005 128 4 907 921 2-s2.0-17144404527 10.1053/j.gastro.2004.12. 036 (Pubitemid 40523543)
105. Kruse M. L., Hopf-Jensen S., Timke C., Differentiation potential of pancreatic fibroblastoid cells/stellate cells: effects of peroxisome proliferator-activated receptor gamma ligands. International Journal of Cell Biology 2011 2011 11 816791
106. Kalluri R., Weinberg R. A., The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation 2009 119 6 1420 1428 2-s2.0-67650999875 10.1172/JCI39104
107. López-Nouoa J. M., Nieto M. A., Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Molecular Medicine 2009 1 6-7 303 314 2-s2.0-70450142560 10.1002/emmm.200900043
108. Mani S. A., Guo W., Liao M. J., Eaton E. N., Ayyanan A., Zhou A. Y., Brooks M., Reinhard F., Zhang C. C., Shipitsin M., Campbell L. L., Polyak K., Brisken C., Yang J., Weinberg R. A., The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008 133 4 704 715 2-s2.0-43049165453 10.1016/j.cell.2008.03.027 (Pubitemid 351636299)
109. Hamada S., Masamune A., Takikawa T., Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells. Biochemical and Biophysical Research Communications 2012 421 2 349 354
110. Kikuta K., Masamune A., Watanabe T., Ariga H., Itoh H., Hamada S., Satoh K., Egawa S., Unno M., Shimosegawa T., Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells. Biochemical and Biophysical Research Communications 2010 403 3-4 380 384 2-s2.0-78650175637 10.1016/j.bbrc.2010.11.040
111. Voutsadakis I. A., Ubiquitination and the ubiquitin-proteasome system as regulators of transcription and transcription factors in epithelial mesenchymal transition of cancer. Tumour Biology 2012 33 4 897 910
112. Voutsadakis I. A., The ubiquitin-proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer. Journal of Biomedical Science 2012 19 67 1 13
113. Reka A. K., Kurapati H., Narala V. R., Bommer G., Chen J., Standiford T. J., Keshamouni V. G., Peroxisome proliferator-activated receptor- γ activation inhibits tumor metastasis by antagonizing smad3-mediated epithelial-mesenchymal transition. Molecular Cancer Therapeutics 2010 9 12 3221 3232 2-s2.0-78650450648 10.1158/1535-7163.MCT-10-0570
114. Chen L., Necela B. M., Su W., Yanagisawa M., Anastasiadis P. Z., Fields A. P., Thompson E. A., Peroxisome proliferator-activated receptor γ promotes epithelial to mesenchymal transformation by Rho GTPase-dependent activation of ERK1/2. Journal of Biological Chemistry 2006 281 34 24575 24587 2-s2.0-33747682898 10.1074/jbc.M604147200 (Pubitemid 44274232)
115. Gupta R. A., DuBois R. N., Controversy: PPAR γ a target for treatment of colorectal cancer. American Journal of Physiology 2002 283 2 G266 G269 2-s2.0-0036077277 (Pubitemid 34791291)
116. Scheen A. J., Hepatotoxicity with thiazolidinediones: is it a class effect? Drug Safety 2001 24 12 873 888 2-s2.0-0035169430 (Pubitemid 33078194)
117. Azoulay L., Yin H., Filion K. B., The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. British Medical Journal 2012 344 e3645 10.1136/bmj.e3645
118. Koga H., Selvendiran K., Sivakumar R., PPAR γ potentiates anticancer effects of gemcitabine on human pancreatic cancer cells. International Journal of Oncology 2012 40 3 679 685
119. Girnun G. D., Naseri E., Vafai S. B., Qu L., Szwaya J. D., Bronson R., Alberta J. A., Spiegelman B. M., Synergy between PPAR γ ligands and platinum-based drugs in cancer. Cancer Cell 2007 11 5 395 406 2-s2.0-34247558604 10.1016/j.ccr.2007.02.025 (Pubitemid 46670076)
120. Galli A., Mello T., Ceni E., Surrenti E., Surrenti C., The potential of antidiabetic thiazolidinediones for anticancer therapy. Expert Opinion on Investigational Drugs 2006 15 9 1039 1049 2-s2.0-33748167914 10.1517/13543784.15.9.1039 (Pubitemid 44314656)
121. Chanan-Khan A. A., Borrello I., Lee K. P., Reece D. E., Development of target-specific treatments in multiple myeloma. British Journal of Haematology 2010 151 1 3 15 2-s2.0-77956814361 10.1111/j.1365-2141.2010.08262.x
122. Awasthi N., Schwarz M. A., Schwarz R. E., Proteasome inhibition enhances antitumour effects of gemcitabine in experimental pancreatic cancer. HPB 2009 11 7 600 605 2-s2.0-73349129983 10.1111/j.1477-2574.2009.00109.x
123. Alberts S. R., Foster N. R., Morton R. F., Kugler J., Schaefer P., Wiesenfeld M., Fitch T. R., Steen P., Kim G. P., Gill S., PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group (NCCTG) randomized phase II study. Annals of Oncology 2005 16 10 1654 1661 2-s2.0-27144435616 10.1093/annonc/mdi324 (Pubitemid 41510140)
124. Wang M., Medeiros B. C., Erba H. P., DeAngelo D. J., Giles F. J., Swords R. T., Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer. Expert Opinion on Therapeutic Targets 2011 15 3 253 264 2-s2.0-79951663751 10.1517/14728222.2011.550877
125. Dickens M. P., Fitzgerald R., Fischer P. M., Small-molecule inhibitors of MDM2 as new anticancer therapeutics. Seminars in Cancer Biology 2010 20 1 10 18 2-s2.0-77952550955 10.1016/j.semcancer.2009.10.003