Sulfatase and aromatase pathway (Homo sapiens)
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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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Ontology Terms
Pathway Ontology : disease pathway
Disease : congenital heart disease oculocerebrorenal syndrome male infertility juvenile myoclonic epilepsy Senior-Loken syndrome Pallister-Hall syndrome Bardet-Biedl syndrome sensorineural hearing loss Carpenter syndrome hydrolethalus syndrome cone-rod dystrophy asphyxiating thoracic dystrophy holoprosencephaly nephronophthisis orofaciodigital syndrome infertility ciliopathy retinitis pigmentosa Leber congenital amaurosis Greig cephalopolysyndactyly syndrome primary ciliary dyskinesia Meckel syndrome Ellis-Van Creveld syndrome medulloblastoma lethal congenital contracture syndrome Birt-Hogg-Dube syndrome polycystic kidney disease Joubert syndrome
Bibliography
- 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
- 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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External references
DataNodes
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Annotated Interactions
Source ![]() | Target ![]() | Type ![]() | Database reference ![]() | Comment ![]() |
---|---|---|---|---|
DHEA | DHEA-S | mim-conversion | 51216 (Rhea) ![]() | |
Estradiol-17beta | estradiol 3-sulphate | mim-conversion | 51076 (Rhea) ![]() | |
estrone | estrone sulphate | mim-conversion | 15973 (Rhea) ![]() |