Sulfatase and aromatase pathway (Homo sapiens)

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1, 2Aromatase pathwaySulfatase pathwayNADH dianionestroneestradiol 3-sulphateNAD anionEstradiol-17betaSULT1E1STSHSD17B1HSD3B1SLCO1B1NADPH tetraanionDHEA-SSLCO1B3HSD17B2SLCO4A1PAPESR2DHEACYP19A1SLCO2B1PAPS(4-)AndrostenedioneNADP trianionESR1estrone sulphateHSD17B3SLCO1A2SLCO4C1testosteroneSULT1E1STSNAD anionNADH dianionSTSSULT1E1SLCO1A2estrone sulphateDHEA-SEstradiol-17betaPAPS(4-)PAPPAPPAPS(4-)SLCO1B1SLCO1B3SLCO2B1


Description

The intratumoral production of estradiol-17beta (E2) from circulating steroid hormone precursors plays an essential role in estrogen-related breast and epithelial ovarian cancer (EOC). There are two possible pathways producing E2, one being the sulfatase pathway starting from estrone sulfate, and one being the aromatase pathway which starts with DHEA-S. Both routes rely on two crucial enzymes: STS for estrogen activation and SULT1E1 for inactivation. Research indicates that an increased STS expression and E2 production is associated with cancer progression. However, sulfonation of E2 via SULT1E1 not only reduces proliferative effects of estrogens on hormone-sensitive tumor cells, but also generates water-soluble estrogen sulfates consequently leading to an increased excretion of sulfonated E2. This helps preventing a metabolic activation of the hormone into potentially mutagenic catechol metabolites. Thus, targeting estrogen-modifying enzymes is a potential endocrine therapy strategy for patients with estrogen-sensitive EOC. This pathway is based on Figure 1 from: Mungenast, F., Aust, S., Vergote, I., Vanderstichele, A., Sehouli, J., Braicu, E., Mahner, S., Castillo‑Tong, D. C., Zeillinger, R., Thalhammer, T."Clinical significance of the estrogen-modifying enzymes steroid sulfatase and estrogen sulfotransferase in epithelial ovarian cancer". Oncology Letters 13, no. 6 (2017): 4047-4054. https://doi.org/10.3892/ol.2017.5969

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Bibliography

  1. Mungenast F, Aust S, Vergote I, Vanderstichele A, Sehouli J, Braicu E, Mahner S, Castillo-Tong DC, Zeillinger R, Thalhammer T; ''Clinical significance of the estrogen-modifying enzymes steroid sulfatase and estrogen sulfotransferase in epithelial ovarian cancer.''; Oncol Lett, 2017 PubMed Europe PMC Scholia
  2. Secky L, Svoboda M, Klameth L, Bajna E, Hamilton G, Zeillinger R, Jäger W, Thalhammer T; ''The sulfatase pathway for estrogen formation: targets for the treatment and diagnosis of hormone-associated tumors.''; J Drug Deliv, 2013 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134449view23:54, 21 July 2024EweitzOntology Term : 'disease pathway' added !
134448view23:54, 21 July 2024EweitzOntology Term : 'cancer pathway' added !
126815view09:32, 24 June 2023IsabelWassinkConnected unconnected edge
126806view16:33, 22 June 2023Glattl98STS ID changed to another data source (uniprot-trembl)
126770view12:41, 21 June 2023DeSlMOved cellular compartments to background for clickability
126769view12:40, 21 June 2023DeSlConnected unconnected line for SULT1E1
126754view16:34, 18 June 2023Dorka1999Changed annotations
126684view08:30, 12 June 2023Dorka1999Adding ChEBI ID to PAP
126673view14:15, 11 June 2023Dorka1999Adding transporter family
126654view14:04, 9 June 2023Dorka1999RHEA annotations added
126653view13:57, 9 June 2023Dorka1999Rhea annotations added for SULT1E1s
126652view13:43, 9 June 2023Dorka1999Differentiating between sulfatase and aromatase pathways
126650view09:43, 9 June 2023Glattl98Reference Update
126649view09:39, 9 June 2023Glattl98Reference Update
126648view09:36, 9 June 2023Glattl98Reference Update
126647view08:41, 9 June 2023Glattl98Reference Update
126646view08:39, 9 June 2023Glattl98Reference Update
126645view08:36, 9 June 2023Glattl98Reference Update
126644view08:32, 9 June 2023Glattl98Modified description
126643view08:29, 9 June 2023Glattl98Modified title
126631view15:52, 7 June 2023Dorka1999Adding PAPS and PAP to all SULT1E1
126625view15:28, 7 June 2023Dorka1999Adding a comment for idenifiying metabolite "PAP"
126611view14:43, 7 June 2023Glattl98Added Metabolites; Changes in Nucleus
126609view12:22, 7 June 2023Dorka1999Ontology Term : 'steroid biosynthetic pathway' added !
126606view12:44, 6 June 2023Glattl98Modified description
126605view12:39, 6 June 2023Glattl98Modified description
126604view12:16, 6 June 2023Glattl98Addition of Transporters
126603view11:51, 6 June 2023Glattl98Alignment of Nodes; Addition of References
126602view11:40, 6 June 2023Glattl98Alignment of Nodes
126601view11:24, 6 June 2023Dorka1999Modified description
126600view11:07, 6 June 2023Glattl98Modified description
126599view10:34, 6 June 2023Dorka1999Modified title
126598view10:30, 6 June 2023Dorka1999Ontology Term : 'sex steroids signaling pathway' added !
126597view10:29, 6 June 2023Dorka1999Ontology Term : 'ovary epithelial cancer' added !
126596view10:20, 6 June 2023Glattl98Modified description
126595view10:15, 6 June 2023Dorka1999Modified title
126594view10:13, 6 June 2023Glattl98New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AndrostenedioneMetaboliteCHEBI:16422 (ChEBI)
CYP19A1ProteinP11511 (Uniprot-TrEMBL)
DHEA-SMetaboliteCHEBI:16814 (ChEBI)
DHEAMetaboliteCHEBI:28689 (ChEBI)
ESR1ProteinP03372 (Uniprot-TrEMBL)
ESR2ProteinQ92731 (Uniprot-TrEMBL)
Estradiol-17betaMetaboliteCHEBI:16469 (ChEBI)
HSD17B1ProteinP14061 (Uniprot-TrEMBL)
HSD17B2ProteinP37059 (Uniprot-TrEMBL)
HSD17B3ProteinP37058 (Uniprot-TrEMBL)
HSD3B1ProteinP14060 (Uniprot-TrEMBL)
NAD anionMetaboliteCHEBI:57540 (ChEBI)
NADH dianionMetaboliteCHEBI:57945 (ChEBI)
NADP trianionMetaboliteCHEBI:58349 (ChEBI)
NADPH tetraanionMetaboliteCHEBI:57783 (ChEBI)
PAPMetabolite58343 (ChEBI) Adenosine 3',5'-bismonophosphate
PAPS(4-)MetaboliteCHEBI:58339 (ChEBI)
SLCO1A2ProteinP46721 (Uniprot-TrEMBL)
SLCO1B1ProteinQ9Y6L6 (Uniprot-TrEMBL)
SLCO1B3ProteinQ9NPD5 (Uniprot-TrEMBL)
SLCO2B1ProteinO94956 (Uniprot-TrEMBL)
SLCO4A1ProteinQ96BD0 (Uniprot-TrEMBL)
SLCO4C1ProteinQ6ZQN7 (Uniprot-TrEMBL)
STSGeneProductP08842 (Uniprot-TrEMBL)
SULT1E1ProteinP49888 (Uniprot-TrEMBL)
estradiol 3-sulphateMetaboliteCHEBI:4866 (ChEBI)
estrone sulphateMetaboliteCHEBI:17474 (ChEBI)
estroneMetaboliteCHEBI:17263 (ChEBI)
testosteroneMetaboliteCHEBI:17347 (ChEBI)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
DHEADHEA-Smim-conversion51216 (Rhea)
Estradiol-17betaestradiol 3-sulphatemim-conversion51076 (Rhea)
estroneestrone sulphatemim-conversion15973 (Rhea)
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