Androgen receptor network in prostate cancer (Homo sapiens)

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21SWI / SNFApoptotic pathwaysFKBP5SPRY1FOXA1TranslationMIR21MYCSPINK1MIR21SPINK1TSC1AR3AR* 3-beta-OH-delta-steroid DH & steroid isomerase =*** Estradiol-17-beta DH = DHB****HSD3B2CYP17A1HSD3B1HSD3B1HSD17B717-alpha-OH-ProgesteroneDihydrotestosteroneHSD3B1HSD3B1AndrostenedioneHSD3B1Hydroxyprogesterone aldolaseHSD3B1ProgesteroneEstradiolHSD3B2TestosteroneHSD3B1EstroneHSD3B1HSD3B1AndrostenediolHSD3B1F13BGlucocortocoid synthesisHSD3B1HSD3B1HSD17B4HSD3B1dehydroepiandrosteroneHSD3B1HSD3B1Hydroxyprogesterone aldolaseSteroid-19-HydroxylaseHSD3B2PregnenoloneCYP17A1HSD3B1HSD3B2HSD3B1HSD17B2HSD3B1HSD3B1HSD17B317-alpha-OH-PregnenoloneHSD17B1HSD3B1CholesterolHSD3B1Mineralocortocoid synthesisSteroid-19-HydroxylaseBASC complexRAD50OCT1MSH6p14CDC2p38ATF1ARID1AASK1BRCA1CASP8PLK1ATRBARD1CASP9CDC25BPUMARB1SMAD3NOXA1BLMQ8NBS1CDK4MRE11STAT1CDC25ABCL2AKT1CASP3BACH1TP53CHK2p15JAK1p27MSH2BAXp13KPRKDCCHK1BRCA1MMP1CDK2BADATMSMAD2E2F1MDM2p21TMPRSS2KLK3KLK2NDRG1ABCC4TMPRSS2ERGTMPRSS2ETV4SP1ARID1BSMARCA4SMARCC1SMARCC2SMARCD1SMARCD2SMARCD3ACTL6AACTL6BCDC42pathwayTrancriptionPRHOpathwayTranscriptionof COX2AP-1TranscriptionAnoikisChanges in cytoskeletonand cell mobilityRAC1pathwayAKT pathwayMAP2K1MAP4K1STAT3HGFRAP1APTPN11PTENMAP2K2MAPK1CRKLHRASFOSDOCK1PXNRAPGEF1RAF1SOS1MetJUNPTK2BPIK3CAPAK1ELK1MAPK8CRKGAB1RAP1BRASA1GRB2MAPK3TSC2RHEBMTORRICTORRPTORRPTOR4EBP1MYCEIF4EBP1EIF4E1B3CCND1SPRY2


Description

The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. The AR is important for therapeutic target in prostate cancer, thus many different inhibitors have been developed, primarily targeting the ligand binding domain of the protein, while inhibitors that target the N-terminal domain of the protein are still under development. Description source: Wikipedia

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Bibliography

  1. Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L, Jiang BH; ''MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.''; PLoS One, 2011 PubMed Europe PMC Scholia
  2. Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, von Bergen M, Horn F, Brocke-Heidrich K; ''MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4.''; Oncogene, 2011 PubMed Europe PMC Scholia
  3. Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM; ''The role of SPINK1 in ETS rearrangement-negative prostate cancers.''; Cancer Cell, 2008 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134233view11:42, 17 July 2024EweitzDisentangle interaction, avoid label-interaction occlusion
134232view11:39, 17 July 2024EweitzIncrease font size on all nodes, for readability
134231view11:29, 17 July 2024EweitzEconomize layout
134230view11:21, 17 July 2024EweitzEconomize layout
134229view10:59, 17 July 2024EweitzImprove contrast for readability, standardize case
134228view10:57, 17 July 2024EweitzEconomize layout
134227view10:43, 17 July 2024EweitzEconomize layout
134226view10:30, 17 July 2024EweitzEconomize layout
134225view10:25, 17 July 2024EweitzEconomize layout
134224view10:20, 17 July 2024EweitzEconomize layout
134223view10:13, 17 July 2024EweitzFix modeling, refine interaction connection point
134222view10:08, 17 July 2024EweitzEconomize organelle shape
134216view08:00, 17 July 2024EgonwRemoved template comments
127838view04:43, 23 December 2023EweitzMove two genes back into circle, refine case
127837view04:38, 23 December 2023EweitzFurther economize layout
127836view03:39, 23 December 2023EweitzFurther economize layout
127834view03:13, 23 December 2023EweitzEconomize layout, fix typo
125525view17:04, 25 February 2023EgonwUpdated a data source
123536view14:39, 2 August 2022EgonwMade two pathways clickable
121719view15:54, 26 February 2022EweitzRefine case, use gene symbols
116551view12:49, 7 May 2021EweitzModified title
115243view17:15, 7 February 2021EgonwReplaced links to a deleted pathway with an equivalent existing pathway
108261view14:47, 3 December 2019L DupuisConnected unconnected line
108107view10:17, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
106708view13:14, 17 September 2019MaintBotHMDB identifier normalization
98360view06:13, 24 August 2018EgonwUpdated the MIR21 identifier.
98155view13:48, 26 July 2018Fehrhartlayout
96290view15:39, 7 March 2018Fehrhartconnected lines-replace by graphic item
96015view15:04, 15 February 2018MkutmonModified description
96014view15:03, 15 February 2018MkutmonModified description
96013view15:00, 15 February 2018MkutmonModified title
85556view08:33, 29 May 2016EgonwReplaced a mim-conversion with Arrow.
84985view18:49, 4 April 2016AlexanderPicoreplaced mim-conversion with mim-transcription-translation for gene to protein
80439view20:55, 22 June 2015KhanspersAdded mir21 targeting of SMARCA4
80426view18:58, 22 June 2015KhanspersAdded mir21 targeting of PTEN and connected interactions
79838view07:57, 18 April 2015EgonwFixed the metabolite label.
79823view07:44, 17 April 2015EgonwReplaced "EC Number" with "Enzyme Nomenclature" as data source (fixing the links out).
73838view00:09, 26 February 2014MaintBotupdated schema
71495view19:19, 17 October 2013MaintBotUpdated data sources
69730view08:23, 11 July 2013EgonwHydroxyprogesterone aldolase is not a metabolite.
67609view11:32, 26 June 2013DdiglesOntology Term : 'prostate cancer pathway' added !
59165view18:25, 22 February 2013MaintBotUpdated Ensembl data source
54728view19:59, 7 December 2012MaintBotadded p38
54672view21:25, 6 December 2012RobertbaertschPeriodical save, work in progress
54277view20:35, 26 November 2012RobertbaertschPeriodical save, work in progress
54276view20:15, 26 November 2012RobertbaertschPeriodical save, work in progress
54275view19:39, 26 November 2012RobertbaertschPeriodical save, work in progress
54241view08:35, 24 November 2012RobertbaertschPeriodical save, work in progress
53136view01:55, 30 October 2012MaintBotModified categories
50365view22:16, 13 August 2012PgfebboOntology Term : 'prostate cancer' added !

External references

DataNodes

View all...
NameTypeDatabase referenceComment
17-alpha-OH-PregnenoloneMetaboliteHMDB0000363 (HMDB)
17-alpha-OH-ProgesteroneMetaboliteHMDB0000374 (HMDB)
4EBP1ProteinQ13541 (Uniprot-TrEMBL)
ABCC4GeneProduct10257 (Entrez Gene)
ACTL6AGeneProduct86 (Entrez Gene)
ACTL6BGeneProduct51412 (Entrez Gene)
AKT1ProteinP31749 (Uniprot-TrEMBL)
ARProtein367 (Entrez Gene) AR
ARID1AGeneProduct8289 (Entrez Gene)
ARID1BGeneProduct57492 (Entrez Gene)
ASK1Protein
ATF1GeneProduct466 (Entrez Gene)
ATMProteinQ13315 (Uniprot-TrEMBL)
ATRProteinQ13535 (Uniprot-TrEMBL)
AndrostenediolMetaboliteHMDB0005849 (HMDB)
AndrostenedioneMetabolite63-05-8 (CAS)
BACH1Protein
BADProteinQ92934 (Uniprot-TrEMBL)
BARD1ProteinQ99728 (Uniprot-TrEMBL)
BAXProteinQ07812 (Uniprot-TrEMBL)
BCL2ProteinP10415 (Uniprot-TrEMBL)
BLMProteinP54132 (Uniprot-TrEMBL)
BRCA1ProteinP38398 (Uniprot-TrEMBL)
CASP3ProteinP42574 (Uniprot-TrEMBL)
CASP8ProteinQ14790 (Uniprot-TrEMBL)
CASP9ProteinP55211 (Uniprot-TrEMBL)
CCND1ProteinP24385 (Uniprot-TrEMBL)
CDC25AGeneProductENSG00000164045 (Ensembl)
CDC25BGeneProductENSG00000101224 (Ensembl)
CDC2ProteinP06493 (Uniprot-TrEMBL) Oncogene
CDK2ProteinP24941 (Uniprot-TrEMBL)
CDK4ProteinP11802 (Uniprot-TrEMBL)
CHK1ProteinO14757 (Uniprot-TrEMBL)
CHK2ProteinO96017 (Uniprot-TrEMBL) Phosphrylated
CRKGeneProduct1398 (Entrez Gene)
CRKLGeneProduct1399 (Entrez Gene)
CYP17A1GeneProduct1586 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
DOCK1GeneProduct1793 (Entrez Gene) Interim Symbol: Dock1 predicted and Name: dedicator of cyto-kinesis 1 (predicted)
DihydrotestosteroneMetaboliteHMDB0002961 (HMDB)
E2F1ProteinQ01094 (Uniprot-TrEMBL)
EIF4E1BProteinA6NMX2 (Uniprot-TrEMBL)
EIF4EBP1GeneProduct1978 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
ELK1GeneProduct2002 (Entrez Gene)
ERGGeneProduct2078 (Entrez Gene) Fusion partner with TMPRSS2 in about 40% of prostate cancers
ETV4GeneProduct2118 (Entrez Gene) Fusion partner with TMPRSS2 in about 40% of prostate cancers
EstradiolMetabolite57-91-0 (CAS)
EstroneMetabolite53-16-7 (CAS)
F13BGeneProduct2165 (Entrez Gene)
FKBP5Protein2289 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene)
FOXA1Protein3169 (Entrez Gene) DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
GAB1GeneProduct2549 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
Glucocortocoid synthesisPathwayWP4523 (WikiPathways)
HGFGeneProduct3082 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
HSD17B1GeneProduct3292 (Entrez Gene)
HSD17B2GeneProduct3294 (Entrez Gene)
HSD17B3GeneProduct3293 (Entrez Gene)
HSD17B4GeneProduct3295 (Entrez Gene)
HSD17B7GeneProduct51478 (Entrez Gene)
HSD3B1GeneProduct3283 (Entrez Gene)
HSD3B2GeneProduct3284 (Entrez Gene)
Hydroxyprogesterone aldolaseGeneProduct4.1.2.30 (Enzyme Nomenclature)
JAK1ProteinP23458 (Uniprot-TrEMBL)
JUNGeneProduct3725 (Entrez Gene)
KLK2GeneProduct3817 (Entrez Gene)
KLK3GeneProduct354 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAP4K1GeneProduct11184 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MDM2ProteinQ00987 (Uniprot-TrEMBL) Oncogene
MIR21RnaENSG00000284190 (Ensembl)
MMP1ProteinP03956 (Uniprot-TrEMBL)
MRE11ProteinP49959 (Uniprot-TrEMBL)
MSH2ProteinP43246 (Uniprot-TrEMBL)
MSH6ProteinP52701 (Uniprot-TrEMBL)
MTORProteinP42345 (Uniprot-TrEMBL)
MYCGeneProduct4609 (Entrez Gene)
MYCProteinP01106 (Uniprot-TrEMBL)
MetGeneProduct24553 (Entrez Gene)
Mineralocortocoid synthesisPathwayWP4523 (WikiPathways)
NDRG1GeneProduct10397 (Entrez Gene)
NOXA1ProteinQ86UR1 (Uniprot-TrEMBL)
OCT1Protein
PAK1GeneProduct5058 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PLK1GeneProductENSG00000166851 (Ensembl)
PRKDCProteinP78527 (Uniprot-TrEMBL)
PTENGeneProduct5728 (Entrez Gene)
PTK2BGeneProduct2185 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
PUMAProtein
PXNGeneProduct5829 (Entrez Gene)
PregnenoloneMetabolite145-13-1 (CAS)
ProgesteroneMetabolite57-83-0 (CAS)
Q8NBS1ProteinQ8NBS1 (Uniprot-TrEMBL)
RAD50ProteinQ92878 (Uniprot-TrEMBL)
RAF1GeneProduct5894 (Entrez Gene)
RAP1AGeneProduct5906 (Entrez Gene)
RAP1BGeneProduct5908 (Entrez Gene)
RAPGEF1GeneProduct2889 (Entrez Gene)
RASA1GeneProduct5921 (Entrez Gene)
RB1ProteinP06400 (Uniprot-TrEMBL)
RHEBProteinQ15382 (Uniprot-TrEMBL)
RICTORProtein253260 (Entrez Gene)
RPTORProteinQ8N122 (Uniprot-TrEMBL)
SMAD2ProteinQ15796 (Uniprot-TrEMBL) Tumor supressor
SMAD3ProteinP84022 (Uniprot-TrEMBL)
SMARCA4GeneProduct6597 (Entrez Gene)
SMARCC1GeneProduct6599 (Entrez Gene)
SMARCC2GeneProduct6601 (Entrez Gene)
SMARCD1GeneProduct6602 (Entrez Gene)
SMARCD2GeneProduct6603 (Entrez Gene)
SMARCD3GeneProduct6604 (Entrez Gene)
SOS1GeneProduct6654 (Entrez Gene) Son of sevenless homolog 1 (Drosophila) (predicted)
SP1Protein6667 (Entrez Gene) DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
SPINK1GeneProduct6690 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
SPINK1ProteinD6RIU5 (Uniprot-TrEMBL)
SPRY1GeneProduct10252 (Entrez Gene)
SPRY2GeneProduct10253 (Entrez Gene)
STAT1ProteinP42224 (Uniprot-TrEMBL)
STAT3GeneProduct6774 (Entrez Gene)
Steroid-19-HydroxylaseGeneProductENSG00000120054 (Ensembl)
TMPRSS2GeneProduct7113 (HGNC Accession number)
TP53ProteinP04637 (Uniprot-TrEMBL)
TSC1ProteinQ92574 (Uniprot-TrEMBL)
TSC2ProteinP49815 (Uniprot-TrEMBL)
TestosteroneMetabolite58-22-0 (CAS)
Translation
dehydroepiandrosteroneMetabolite53-43-0 (CAS)
p13KProtein
p14Protein
p15Protein
p21Protein
p27Protein
p38GeneProductENSG00000112062 (Ensembl)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2263"
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