KEGG   PATHWAY: ppam05215
Entry
ppam05215                   Pathway                                
Name
Prostate cancer - Pteronotus mesoamericanus (Parnell's mustached bat)
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
ppam05215  Prostate cancer
ppam05215

Disease
H00024  Prostate cancer
Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129061268  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
129062359  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
129062388  CREB3L4; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
129062851  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
129062984  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129063111  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
129063946  NRAS; GTPase NRas [KO:K07828]
129064059  SPINT1; LOW QUALITY PROTEIN: kunitz-type protease inhibitor 1 [KO:K15619]
129064134  [KO:K03099]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129064678  PLAT; LOW QUALITY PROTEIN: tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
129064790  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
129064807  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
129064826  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
129065155  [KO:K04079]
129065223  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
129065324  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
129066034  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129066210  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066549  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
129066685  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129067419  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129067491  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
129067827  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
129068119  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
129068348  [KO:K23790]
129068349  [KO:K23790]
129068502  INS; insulin [KO:K04526]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129068571  RELA; transcription factor p65 [KO:K04735]
129068612  BAD; bcl2-associated agonist of cell death [KO:K02158]
129068919  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129068981  E2F2; transcription factor E2F2 [KO:K09389]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129069640  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129069750  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
129069768  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
129070296  SLC46A1; LOW QUALITY PROTEIN: proton-coupled folate transporter [KO:K14613]
129070437  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
129070474  E2F1; transcription factor E2F1 [KO:K17454]
129071120  AR; androgen receptor [KO:K08557]
129071373  HSP90B1; endoplasmin [KO:K09487]
129071377  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129072575  PDGFC; platelet-derived growth factor C [KO:K05450]
129072618  [KO:K13649]
129072619  [KO:K13649]
129072620  FOLR2; folate receptor beta [KO:K13649]
129072719  [KO:K13649]
129072823  GRM5; metabotropic glutamate receptor 5 isoform X1 [KO:K04604]
129072829  FOLH1; glutamate carboxypeptidase 2 [KO:K14592] [EC:3.4.17.21]
129072878  SLC19A1; reduced folate transporter [KO:K14609]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129073949  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129074243  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
129074378  IKBKG; NF-kappa-B essential modulator [KO:K07210]
129074550  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129074669  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
129074892  NKX3-1; LOW QUALITY PROTEIN: homeobox protein Nkx-3.1 [KO:K09348]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129075586  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129075656  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129075868  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
129076239  [KO:K04079]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129076927  [KO:K04079]
129077110  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129077183  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129077222  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
129077631  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
129077836  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129077851  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
129077932  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078156  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
129078764  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129079431  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129079853  ETV5; ETS translocation variant 5 [KO:K15593]
129079949  [KO:K04079]
129080390  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129080730  [KO:K04079]
129080865  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129080954  FOXO1; forkhead box protein O1 [KO:K07201]
129081363  TGFA; protransforming growth factor alpha [KO:K08774]
129081516  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129082066  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129082282  [KO:K04079]
129083615  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
129083641  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
129083921  [KO:K04079]
129084214  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129085013  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
129085287  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129085299  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129085322  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129085787  E2F3; transcription factor E2F3 [KO:K06620]
129085829  ZEB1; zinc finger E-box-binding homeobox 1 [KO:K09299]
129085846  [KO:K04079]
129085920  [KO:K04079]
129086014  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
129086041  [KO:K01394] [EC:3.4.24.17]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129086587  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129087036  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
129088214  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
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
ppam00140  Steroid hormone biosynthesis
ppam04010  MAPK signaling pathway
ppam04060  Cytokine-cytokine receptor interaction
ppam04110  Cell cycle
ppam04115  p53 signaling pathway
ppam04151  PI3K-Akt signaling pathway
ppam04210  Apoptosis
ppam04981  Folate transport and metabolism
ppam05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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