KEGG   PATHWAY: pvp05215
Entry
pvp05215                    Pathway                                
Name
Prostate cancer - Pteropus vampyrus (large flying fox)
Description
Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.
Class
Human Diseases; Cancer: specific types
Pathway map
pvp05215  Prostate cancer
pvp05215

Disease
H00024  Prostate cancer
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288383  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105288497  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
105288645  SPINT1; kunitz-type protease inhibitor 1 [KO:K15619]
105288867  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289441  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
105290070  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105290270  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
105290328  CTNNB1; catenin beta-1 [KO:K02105]
105290449  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105291441  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
105291480  TCF7L2; transcription factor 7-like 2 isoform X8 [KO:K04491]
105291624  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105291659  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105291925  SLC46A1; proton-coupled folate transporter [KO:K14613]
105292199  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
105292717  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293004  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293045  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105293112  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105293217  [KO:K09047]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293567  TCF7; transcription factor 7 isoform X2 [KO:K02620]
105293808  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
105293923  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294194  FOLH1B; putative N-acetylated-alpha-linked acidic dipeptidase isoform X1 [KO:K14592] [EC:3.4.17.21]
105294211  GRM5; metabotropic glutamate receptor 5 [KO:K04604]
105294412  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294593  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
105295757  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
105296333  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
105296460  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297140  [KO:K02649]
105297442  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
105297467  [KO:K01394] [EC:3.4.24.17]
105297848  BAD; bcl2-associated agonist of cell death [KO:K02158]
105297999  RELA; transcription factor p65 [KO:K04735]
105298051  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105298078  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
105298192  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105298312  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
105298404  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105298541  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298726  IL1R2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
105298901  FOXO1; forkhead box protein O1 [KO:K07201]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299142  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
105299280  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299436  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
105299625  AR; LOW QUALITY PROTEIN: androgen receptor [KO:K08557]
105300023  RB1; retinoblastoma-associated protein [KO:K06618]
105300159  [KO:K04456] [EC:2.7.11.1]
105300315  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105300517  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
105300585  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
105301022  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301329  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105302532  IKBKG; NF-kappa-B essential modulator [KO:K07210]
105302600  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105302792  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105303098  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105303144  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105303182  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105303657  FOLR2; folate receptor beta [KO:K13649]
105303658  [KO:K13649]
105303691  [KO:K13649]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304277  E2F1; transcription factor E2F1 [KO:K17454]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304619  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105304705  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
105305241  ERG; transcriptional regulator ERG [KO:K09435]
105305459  ARAF; serine/threonine-protein kinase A-Raf isoform X8 [KO:K08845] [EC:2.7.11.1]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105305966  SLC19A1; LOW QUALITY PROTEIN: folate transporter 1 [KO:K14609]
105306141  [KO:K04361] [EC:2.7.10.1]
105306466  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
105306557  [KO:K23790]
105306558  [KO:K23790]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105306745  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105306821  ETV5; ETS translocation variant 5 [KO:K15593]
105307128  [KO:K04503]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307498  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308799  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
105310743  HSP90B1; endoplasmin [KO:K09487]
Compound
C00025  L-Glutamate
C00280  Androstenedione
C00410  Progesterone
C00504  Folate
C00535  Testosterone
C00735  Cortisol
C00762  Cortisone
C00951  Estradiol-17beta
C01042  N-Acetyl-L-aspartate
C01227  Dehydroepiandrosterone
C03917  Dihydrotestosterone
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07653  Flutamide
C12270  N-Acetylaspartylglutamate
C16038  2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Reference
PMID:12878745
  Authors
Nelson WG, De Marzo AM, Isaacs WB.
  Title
Prostate cancer.
  Journal
N Engl J Med 349:366-81 (2003)
DOI:10.1056/NEJMra021562
Reference
PMID:15724144
  Authors
Li L, Ittmann MM, Ayala G, Tsai MJ, Amato RJ, Wheeler TM, Miles BJ, Kadmon D, Thompson TC.
  Title
The emerging role of the PI3-K-Akt pathway in prostate cancer progression.
  Journal
Prostate Cancer Prostatic Dis 8:108-18 (2005)
DOI:10.1038/sj.pcan.4500776
Reference
PMID:16551847
  Authors
Pienta KJ, Bradley D.
  Title
Mechanisms underlying the development of androgen-independent prostate cancer.
  Journal
Clin Cancer Res 12:1665-71 (2006)
DOI:10.1158/1078-0432.CCR-06-0067
Reference
PMID:11900250
  Authors
Feldman BJ, Feldman D.
  Title
The development of androgen-independent prostate cancer.
  Journal
Nat Rev Cancer 1:34-45 (2001)
DOI:10.1038/35094009
Reference
PMID:15082523
  Authors
Heinlein CA, Chang C.
  Title
Androgen receptor in prostate cancer.
  Journal
Endocr Rev 25:276-308 (2004)
DOI:10.1210/er.2002-0032
Reference
PMID:9422516
  Authors
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP.
  Title
Androgen receptor gene and hormonal therapy failure of prostate cancer.
  Journal
Am J Pathol 152:1-9 (1998)
Reference
PMID:10835690
  Authors
Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D.
  Title
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.
  Journal
Nat Med 6:703-6 (2000)
DOI:10.1038/76287
Reference
PMID:10453277
  Authors
Macri E, Loda M.
  Title
Role of p27 in prostate carcinogenesis.
  Journal
Cancer Metastasis Rev 17:337-44 (1998)
DOI:10.1023/A:1006133620914
Reference
PMID:11750244
  Authors
Steers WD.
  Title
5alpha-reductase activity in the prostate.
  Journal
Urology 58:17-24; discussion 24 (2001)
DOI:10.1016/S0090-4295(01)01299-7
Reference
PMID:8069858
  Authors
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF.
  Title
Effects of human and rat glutathione S-transferases on the covalent DNA binding of the N-acetoxy derivatives of heterocyclic amine carcinogens in vitro: a possible mechanism of organ specificity in their carcinogenesis.
  Journal
Cancer Res 54:4920-6 (1994)
Reference
PMID:11527574
  Authors
Grimes CA, Jope RS.
  Title
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
  Journal
Prog Neurobiol 65:391-426 (2001)
DOI:10.1016/S0301-0082(01)00011-9
Reference
PMID:21747944
  Authors
Leshem O, Madar S, Kogan-Sakin I, Kamer I, Goldstein I, Brosh R, Cohen Y, Jacob-Hirsch J, Ehrlich M, Ben-Sasson S, Goldfinger N, Loewenthal R, Gazit E, Rotter V, Berger R
  Title
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
  Journal
PLoS One 6:e21650 (2011)
DOI:10.1371/journal.pone.0021650
Reference
PMID:20478527
  Authors
Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM
  Title
An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
  Journal
Cancer Cell 17:443-54 (2010)
DOI:10.1016/j.ccr.2010.03.018
Reference
PMID:19399032
  Authors
Squire JA
  Title
TMPRSS2-ERG and PTEN loss in prostate cancer.
  Journal
Nat Genet 41:509-10 (2009)
DOI:10.1038/ng0509-509
Reference
PMID:25915839
  Authors
Adamo P, Ladomery MR
  Title
The oncogene ERG: a key factor in prostate cancer.
  Journal
Oncogene 35:403-14 (2016)
DOI:10.1038/onc.2015.109
Reference
PMID:25485532
  Authors
Burdova A, Bouchal J, Tavandzis S, Kolar Z
  Title
TMPRSS2-ERG gene fusion in prostate cancer.
  Journal
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 158:502-10 (2014)
DOI:10.5507/bp.2014.065
Reference
PMID:18172298
  Authors
Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
  Title
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
  Journal
Cancer Res 68:73-80 (2008)
DOI:10.1158/0008-5472.CAN-07-5352
Reference
PMID:28968951
  Authors
Kim H, Datta A, Talwar S, Saleem SN, Mondal D, Abdel-Mageed AB
  Title
Estradiol-ERbeta2 signaling axis confers growth and migration of CRPC cells through TMPRSS2-ETV5 gene fusion.
  Journal
Oncotarget 8:62820-62833 (2017)
DOI:10.18632/oncotarget.11355
Reference
PMID:38977769
  Authors
Bakht MK, Beltran H
  Title
Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.
  Journal
Nat Rev Urol 22:26-45 (2025)
DOI:10.1038/s41585-024-00900-z
Related
pathway
pvp00140  Steroid hormone biosynthesis
pvp04010  MAPK signaling pathway
pvp04060  Cytokine-cytokine receptor interaction
pvp04110  Cell cycle
pvp04115  p53 signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04210  Apoptosis
pvp04981  Folate transport and metabolism
pvp05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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