Advertisement

The p38 MAPK Pathway in Prostate Cancer

  • Daniel Djakiew
Chapter
Part of the Protein Reviews book series (PRON, volume 16)

Abstract

The conventional signal transduction pathway for p38 MAPK is complex and diverse. A plethora of signals such as growth factors interact with death receptors to initiate a biochemical cascade by recruitment of activator molecules that in combination activate MAP3Ks. Many drugs intercede at the level of signal, activator, or MAP3Ks to mimic initiation of the signal transduction cascade. In the prostate, these signaling moieties, which include NSAIDs, converge at the level of MAP2Ks, ostensibly MKK6, which phosphorylates up to 4 isoforms of p38 MAPK. Phosphatases such as MKP1 or compounds such as biochanin A are able to antagonize activation of p38 MAPK. Phosphorylation of p38 MAPK allows phosphorylation of MK2 and MK3 that in turn promote stability of the p75NTR transcript. Concurrently, translocation of HuR from the nucleus to the cytoplasm and increased levels of HuR and eIF4E also promote p75NTR mRNA stability and increased levels of the p75NTR protein. In the prostate, the p75NTR functions as both a tumor and metastasis suppressor. In this context, increased expression of p75NTR modulates cell cycle effectors producing cytostasis in G0/G1, as well as mitochondrial effectors that modulate a caspase cascade leading to apoptosis. In addition, increased expression of p75NTR modulates motility effectors, ostensibly NAG-1, that retards cell migration. Hence, activation of the p38 MAPK pathway through a plethora of signal initiating events, leads to tumor and metastasis suppressor activity in prostate cancer cells.

Keywords

Prostate Cancer Cell Inhibit Cell Migration Reduce Cell Migration p75NTR Expression Initiate Signal Transduction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Land Vatter SW, Strickler JE, Megan M, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL, Young PR (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372:739–746PubMedCrossRefGoogle Scholar
  2. 2.
    Casar B, Sanz-Moreno V, Tazicioglu MN, Rodriguez J, Berciano MT, Lafargu M, Cobb MH, Crespo P (2007) Mxi2 promotes stimulus-independent ERK nuclear translocation. EMBO J 26:635–646. doi: 10.1038/sj.emboj.7601523 PubMedCrossRefGoogle Scholar
  3. 3.
    Yagasaki Y, Sudo T, Osada H (2004) Exip, a splicing variant of p38α, participates in interleukin-­1 receptor proximal complex and downregulates NFκB pathway. FEBS Lett 575:136–140. doi: 10.1016/j.physletb.2003.10.071 PubMedCrossRefGoogle Scholar
  4. 4.
    Yong H-Y, Koh M-S, Moon A (2009) The p38 MAPK inhibitors for the treatment of ­inflammatory diseases and cancer. Expert Opin Investig Drug 18:1893–1905. doi: 10.1517/13543780903321490 CrossRefGoogle Scholar
  5. 5.
    Kumar S, Boehm J, Lee JC (2003) p38 MAPK: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2:717–726. doi: 10.1038/nrd1177 PubMedCrossRefGoogle Scholar
  6. 6.
    Keshet Y, Seger R (2010) The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 661:3–38. doi: 10.1007/978-1-60761-795-2_1 PubMedCrossRefGoogle Scholar
  7. 7.
    Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) P38MAPK: stress responses from molecular mechanisms to therapeutics. Trends Mol Med 15:369–379. doi: 10.1016/j.physletb.2003.10.071 PubMedCrossRefGoogle Scholar
  8. 8.
    Cargnello M, Roux PR (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75:50–83. doi: 10.1128/MMBR.00031-10 PubMedCrossRefGoogle Scholar
  9. 9.
    Bradham C, McClay DR (2006) P38 MAPK in development and cancer. Cell Cycle 5:824–828. doi: 10.4161/cc.5.8.2685 PubMedCrossRefGoogle Scholar
  10. 10.
    Zarubin T, Han J (2005) Activation and signaling of the p38 MAP kinase pathway. Cell Res 15:11–18. doi: 10.1038/sj.cr.7290257 PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen DM (2005) SRC family kinases in cell volume regulation. Am J Physiol Cell Physiol 288:C483–C493. doi: 10.1152/ajpcell.00452.2004 PubMedCrossRefGoogle Scholar
  12. 12.
    Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signaling pathways in cancer. Oncogene 26:3279–3290. doi: 10.1038/sj.onc.121042 PubMedCrossRefGoogle Scholar
  13. 13.
    Perregaux DG, Dean D, Cronan M, Connelly P, Gabel CA (1995) Inhibition of interleukin-1 beta production by SKF86002: evidence of two sites of in vitro activity and of a time and system dependence. Mol Pharmacol 48:433–442PubMedGoogle Scholar
  14. 14.
    Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869PubMedGoogle Scholar
  15. 15.
    Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9:537–549. doi: 10.1038/nrc2694 PubMedCrossRefGoogle Scholar
  16. 16.
    Bradley JR, Pober JS (2001) Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 20:6482–6491PubMedCrossRefGoogle Scholar
  17. 17.
    Goldsmith ZG, Dhanasekaran DN (2007) G protein regulation of MAPK networks. Oncogene 26:3122–3142. doi: 10.1038/sj.onc.1210407 PubMedCrossRefGoogle Scholar
  18. 18.
    Bagrodia S, Derijard B, Davis RJ, Cerione RA (1995) Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 MAPK mitogen-activated protein kinase activation. J Biol Chem 270:27995–27998. doi: 10.1074/jbc.270.47.27995 PubMedCrossRefGoogle Scholar
  19. 19.
    Turpaev KT (2002) Reactive oxygen species and regulation of gene expression. Biochemistry (Mosc) 67:281–292CrossRefGoogle Scholar
  20. 20.
    Nakao N, Kurokawa T, Nomami T, Tumurkhuu G, Koide N, Yokochi T (2008) Hydrogen peroxide induces the production of tumor necrosis factor-alpha in RAW 264.7 macrophage cells via activation of p38 and stress activated protein kinase. Innate Immun 14:190–196. doi: 10.1177/1753425908093932 PubMedCrossRefGoogle Scholar
  21. 21.
    Han J, Lee JD, Jiang Y, Li Z, Feng L, Ulevitch RJ (1996) Characterization of the structure and function of a novel MAP kinase kinase (MKK6). J Biol Chem 271:2886–2891. doi: 10.1074/jbc.271.6.2886 PubMedCrossRefGoogle Scholar
  22. 22.
    Jiang Y, Gram H, Zhao M, New L, Gu J, Feng L, Di Padova F, Ulevitch RJ, Han J (1997) Characterization of the structure and function of the fourth member of p38 group mitogen-­activated protein kinases, p38delta. J Biol Chem 272:30122–30128. doi: 10.1074/jbc.272.48.30122 PubMedCrossRefGoogle Scholar
  23. 23.
    Magi-Galluzzi C, Mishra R, Fiorentino M, Montironi R, Capodieci P, Wishnow K, Kaplan I, Stork PJ, Loda M (1997) Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. Lab Invest 76:37–51PubMedGoogle Scholar
  24. 24.
    Liu Y, Loagowski G, Sundholm A, Sundberg A, Kulesz-Martin M (2007) Microtubule disruption and tumor suppression by mitogen-activated protein kinase phosphatase 4. Cancer Res 67:10711–10719. doi: 10.1158/0008-5472.CAN-07-1968 PubMedCrossRefGoogle Scholar
  25. 25.
    Takekawa M, Adachi M, Nakahata A, Nakayama I, Itoh F, Tsukuda H, Taya Y, Imai K (2000) p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J 19:6517–6526. doi: 10.1093/emboj/19.23.6517 PubMedCrossRefGoogle Scholar
  26. 26.
    Zanke B, Squire J, Griesser H, Henry M, Suzuki H, Patterson B, Minden M, Mak TW (1994) A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1. Leukemia 8:236–244PubMedGoogle Scholar
  27. 27.
    Yin Y, Liu Y-X, Jin Y, Hall E, Barret J (2003) PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature 422:527–531. doi: 10.1038/nature01519 PubMedCrossRefGoogle Scholar
  28. 28.
    Lammes T, Peschke P, Ehemann V, Debus J, Slobodin B, Lavis S, Huber P (2007) Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity. Mol Cancer 6:65–79. doi: 10.1186/1476-4598-6-65 CrossRefGoogle Scholar
  29. 29.
    Han J, Sun P (2007) The pathways to tumor suppression via route p38. Trends Biochem Sci 32:364–371. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  30. 30.
    Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T, Nebreda AR (1994) A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78:1027–1037. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  31. 31.
    Kotlyarov A, Neininger A, Schubert C, Eckert R, Birchmeier C, Volk HD, Gaestel M (1999) MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis. Nat Cell Biol 1:94–97. doi: 10.1038/10061 PubMedCrossRefGoogle Scholar
  32. 32.
    Han Q, Leng J, Bian D, Mahanivong C, Carpenter KA, Pan ZK, Han J, Huang S (2002) Rac1-­MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activattor mRNA stability in invasive breast cancer cells. J Biol Chem 277:48379–48385. doi: 10.1074/jbc.M209542200 PubMedCrossRefGoogle Scholar
  33. 33.
    Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, Ludwig S, Rapp UR (2000) Serine/threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor E47 and repress its transcriptional activity. J Biol Chem 275:20239–20242. doi: 10.1074/jbc.C901040199 PubMedCrossRefGoogle Scholar
  34. 34.
    Yannoni Y, Gaestel M, Lin LL (2004) P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity. FEBS Lett 564:205–211. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  35. 35.
    Voncken JW, Niessen H, Neufeld B, Rennefahrt U, Dahlmans V, Kubben N, Holzer B, Ludwig S, Rapp UR (2005) MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1. J Biol Chem 280:5178–5187. doi: 10.1074/jbc.M407155200 PubMedCrossRefGoogle Scholar
  36. 36.
    Manke IA, Nguyen A, Lim D, Stewart MQ, Elia AE, Yaffe MB (2005) MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV radiation. Mol Cell 17:37–48. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  37. 37.
    Bulavin DV, Fornace AJ (2004) P38 MAP kinases’s emerging role as a tumor suppressor. Adv Cancer Res 92:95–118. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  38. 38.
    Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331PubMedCrossRefGoogle Scholar
  39. 39.
    Juo P, Kuo CJ, Reynolds SE, Konz RF, Raingeaud J, Davis RJ, Biemann HP, Blenis J (1997) Fas activation of the p38 mitogen-activated protein kinase signaling pathway requires ICE/CED-3 family proteases. Mol Cell Biol 17:24–35PubMedGoogle Scholar
  40. 40.
    Kummer JL, Rao PK, Heidenreich KA (1997) Apoptosis induced by withdrawl of trophic factors is mediated by p38 mitogen-activated kinase. J Biol Chem 272:20490–20494. doi: 10.1074/jbc.272.33.20490 PubMedCrossRefGoogle Scholar
  41. 41.
    Ambrosino C, Nebreda AR (2001) Cell cycle regulation by 38 MAP kinases. Biol Cell 93:47–51PubMedCrossRefGoogle Scholar
  42. 42.
    Thornton TM, Rincon M (2009) Non-classical p38 MAP kinase functions: cell cycle checkpoints and survival. Int J Biol Sci 5:44–51. doi: 10.7150/ijbs.5.44 PubMedCrossRefGoogle Scholar
  43. 43.
    Haq R, Brenton JD, Takahashi M, Finan D, Finkielsztein A, Damaraju S, Rottapel R, Zanke B (2002) Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescence. Cancer Res 62:5076–5082PubMedGoogle Scholar
  44. 44.
    Olson JM, Hallahan AR (2004) P38 MAP kinase: A convergence point in cancer therapy. Trends Mol Med 10:125–129. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  45. 45.
    Magi-Galluzzi C, Montironi R, Cangi MG, Wishnow K, Loda M (1998) Mitogen-activated protein kinases and apoptosis in PIN. Virchows Arch 432:407–413. doi: 10.1007/s004280050184 PubMedCrossRefGoogle Scholar
  46. 46.
    Royuela M, Arenas I, Bethencourt B, Fraile B, Paniagua R (2002) Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate. Hum Pathol 33:299–306. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  47. 47.
    Uzgare AR, Kaplan PK, Greenberg M (2003) Differential expression and/or activation of p38 MAPK, erk1/2 and jnk during the initiation and progression of prostate cancer. Prostate 55:128–139. doi: 10.1002/pros.1021 PubMedCrossRefGoogle Scholar
  48. 48.
    Ricote M, Carcia-Tunon F, Bethencourt F, Fraile B, Onsurbe P, Paniagua R, Royuela M (2006) The p38 MAPK transduction pathway in prostatic neoplasia. J Pathol 208:401–407. doi: 10.1002/path.1910 PubMedCrossRefGoogle Scholar
  49. 49.
    Chao MV (1994) The p75 neurotrophin receptor. J Neurobiol 25:1373–1385PubMedCrossRefGoogle Scholar
  50. 50.
    Chapman BS (1995) A region of the 75kD neurotrophin receptor homologous to the death domains of TNFR-1 and Fas. FEBS Lett 374:216–220. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  51. 51.
    Rabizadeh S, Oh J, Zhong LT, Yang J, Bitler CM, Butcher LL, Bredesen DE (1993) Induction of apoptosis by the low-affinity NGF receptor. Science 261:345–348PubMedCrossRefGoogle Scholar
  52. 52.
    Khwaja F, Tabassum A, Allen J, Djakiew D (2006) The p75NTR tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells. Biochem Biophys Res Commun 341:1184–1192. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  53. 53.
    Quann E, Khwaja F, Zavitz KH, Djakiew D (2007) The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res 67:3254–3262. doi: 10.1158/0008-5472.CAN-06-3657 PubMedCrossRefGoogle Scholar
  54. 54.
    Quann E, Khwaja F, Djakiew D (2007) The p38 MAPK Pathway Mediates Aryl Propionic Acid-Induced messenger RNA Stability of p75NTR in Prostate Cancer Cells. Cancer Res 67:11402–11410. doi: 10.1158/0008-5472.CAN-07-1792 PubMedCrossRefGoogle Scholar
  55. 55.
    Khwaja F, Quann E, Pattabiramen S, Wynne S, Djakiew D (2008) Carprofen Induction of p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. Mol Cancer Ther 7:3539–3545. doi: 10.1158/1535-7163.MCT-08-0512 PubMedCrossRefGoogle Scholar
  56. 56.
    Djakiew D (2011) NSAID Induction of p75NTR in the prostate: a suppressor of growth and cell migration via the p38 MAPK Pathway. In: Prostate cancer: original investigation and case studies. ISBN 979-953-307-628-6Google Scholar
  57. 57.
    Shimada K, Nakamura M, Ishida E, Konishi N (2006) Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer. Histol Histopathol 21:415–422PubMedGoogle Scholar
  58. 58.
    Joo SS, Yoo YM (2009) Melatonin induces apoptotic death in LNaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res 47:8–14. doi: 10.1111/j.1600-079X.2009.00682.x PubMedCrossRefGoogle Scholar
  59. 59.
    Vayalil PK, Mittal A, Kayiyar SK (2004) Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with inhibition of activation of MAPK and NKkappaB. Carcinogenesis 25:987–995. doi: 10.1093/carcin/bgh095 PubMedCrossRefGoogle Scholar
  60. 60.
    Zhang YX, Kong CZ (2008) The role of mitogen-activated protein kinase cascades in inhibition of proliferation in human rpstate carcinoma cells by raloxifene: an in vitro experiment. Zhonghua Yi Xue Za Zhi 88:271–275PubMedGoogle Scholar
  61. 61.
    Chang HL, Wu YC, Su H, Yeh T, Yuan SSF (2008) Protoapigenone, a novel falvinoid, induces apoptosis in human prostate cancer cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase ½. J Pharmacol Exp Ther 325:841–849. doi: 10.1124/jpet.107.135442 PubMedCrossRefGoogle Scholar
  62. 62.
    Huang X, Chen S, Xu L, Deb DK, Platanais LC, Bergan RC (2005) Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Res 65:3470–3478. doi: 10.1158/0008-5472.CAN-04-2807 PubMedGoogle Scholar
  63. 63.
    El Touny L, Henderson F, Djakiew D (2010) Biochanin A reduces drug-induced p75NTR expression and enhances cell survival: a new in vitro assay for screening inhibitors of p75NTR expression. Rejuvenation Res 13:527–537. doi: 10.1089/rej.2009.1006 PubMedCrossRefGoogle Scholar
  64. 64.
    Krygier S, Djakiew D (2001) Molecular characterization of the loss of p75(NTR) expression in human prostate tumor cells. Mol Carcinog 31:46–55. doi: 10.1002/mc.1038 PubMedCrossRefGoogle Scholar
  65. 65.
    Sun B, Zhang B, Yonz C, Cummings BS (2010) Inhibition of calcium-independent ­phospholipasealing pathways during cytostasis in prostate cancer cells. Biochem Pharmacol 15:1727–1735. doi: 10.1016/j.bbr.2011.03.031 CrossRefGoogle Scholar
  66. 66.
    Shukla S, Gupta S (2007) Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle 6:1102–1114. doi: 10.4161/cc.6.9.4146 PubMedCrossRefGoogle Scholar
  67. 67.
    Mukhopadhyay I, Sausville EA, Doroshow JH, Roy KK (2006) Molecular mechanism of adaphostin-­mediated G1 arrest in prostate cancer (PC-3) cells: signaling events mediated by hepatocyte growth factor receptor, c-Met, and p38 MAPK pathways. J Biol Chem 281:37330–37344. doi: 10.1074/jbc.M605569200 PubMedCrossRefGoogle Scholar
  68. 68.
    Kim SH, Kim SY, Park EJ, Kim J, Park HH, So I, Kim SJ, Jeon JH (2011) Icilin induces G1 arrest through activating JNK and p38 kinase in a TRPM8-independent manner. Biochem Biophys Res Commun 406:30–35. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  69. 69.
    Krygier S, Djakiew D (2001) The neurotrophin receptor p75NTR is a tumor suppressor in human prostate cancer. Anticancer Res 21:3749–3755PubMedGoogle Scholar
  70. 70.
    Nalbandian A, Pang AL, Rennert OM, Chan W-Y, Ravindranath N, Djakiew D (2005) A novel function of differentiation revealed by cDNA microarray profiling of p75NTR-regulated gene expression. Differentiation 73:385–396. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  71. 71.
    Jiang AL, Zhang PL, Chen WW, Liu WW, Yu CX, Hu XY, Zhang XQ, Zhang JY (2006) Effects of 9-cis retinoic acid on human homeobox gene NKX3.1 expression in prostate cancer cell line LNCaP. Asian J Androl 8:435–441. doi: 10.1111/j.1745-7262.2006.00171.x PubMedCrossRefGoogle Scholar
  72. 72.
    Meyer C, Jacobs H, Lehner C (2002) Cyclin d-cdk4 is not a master regulator of cell multiplication in drosophila embryos. Curr Biol 12:661–666. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  73. 73.
    Harbour J, Dean D (2000) The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev 14:2393–2409. doi: 10.1101/gad.813200 PubMedCrossRefGoogle Scholar
  74. 74.
    Carito V, Pingitore A, Cione E, Perrotta I, Mancuso D, Russo A, Genchi G, Caroleo MC (2011) Localization of nerve growth factor (NGF) receptors in the mitochondrial compartment: characterization and putative role. Biochim Biophys Acta 1820:96–103. doi: 10.1016/j.bbr.2011.03.03 PubMedCrossRefGoogle Scholar
  75. 75.
    Shiozaki EN, Shi Y (2004) Caspases IAPs, and Smac/DIABLO: mechanisms from structural biology. Trends Biochem Sci 29:486–494. doi: 10.1016/j.bbr.2011.03.031 PubMedCrossRefGoogle Scholar
  76. 76.
    Wynne S, Djakiew D (2010) NSAID-inhibition of prostate cancer cell migration is mediated by Nag-1 induction via the p38 MAPK-p75NTR pathway. Mol Cancer Res 8:1656–1664. doi: 10.1158/1541-7786.MCR-10-0342 PubMedCrossRefGoogle Scholar
  77. 77.
    Deziel BA, Patel K, Neto C, Gottschall-Pass K, Hurta RA (2010) Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinases-2 and matrix metalloproteinases-9 activity in human prostate cancer cells via alteractions in mutilpe cellular signaling pathways. J Cell Biochem 111:742–754. doi: 10.1002/jcb.22761 PubMedCrossRefGoogle Scholar
  78. 78.
    Nalbandian A, Djakiew D (2006) The p75NTR metastasis suppressor inhibits urokinase plasminogen activator, matrix metalloproteinase-2 and matrix metalloproteinase-9 in PC-3 prostate cancer cells. Clin Exp Metastasis 23:107–116. doi: 10.1007/s10585-006-9009-y PubMedCrossRefGoogle Scholar

Copyright information

© Mayo Clinic 2013

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular & Cellular BiologyGeorgetown University Medical CenterWashington, DCUSA

Personalised recommendations