Sulfatase and aromatase pathway (WP5368)

Homo sapiens

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

Authors

Lisa Glatt , Dorottya Szobol , Denise Slenter , Isabel Wassink , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

ovary epithelial cancer

Pathway Ontology

cancer pathway disease pathway sex steroids signaling pathway steroid biosynthetic pathway

Participants

Label Type Compact URI Comment
NADH dianion Metabolite chebi:57945
estrone Metabolite chebi:17263
estradiol 3-sulphate Metabolite chebi:4866
NAD anion Metabolite chebi:57540
Estradiol-17beta Metabolite chebi:16469
NADPH tetraanion Metabolite chebi:57783
DHEA-S Metabolite chebi:16814
PAP Metabolite chebi:58343 Adenosine 3',5'-bismonophosphate
DHEA Metabolite chebi:28689
PAPS(4-) Metabolite chebi:58339
Androstenedione Metabolite chebi:16422
NADP trianion Metabolite chebi:58349
estrone sulphate Metabolite chebi:17474
testosterone Metabolite chebi:17347
STS GeneProduct uniprot:P08842
SULT1E1 Protein uniprot:P49888
HSD17B1 Protein uniprot:P14061
HSD3B1 Protein uniprot:P14060
SLCO1B1 Protein uniprot:Q9Y6L6
SLCO1B3 Protein uniprot:Q9NPD5
HSD17B2 Protein uniprot:P37059
SLCO4A1 Protein uniprot:Q96BD0
ESR2 Protein uniprot:Q92731
CYP19A1 Protein uniprot:P11511
SLCO2B1 Protein uniprot:O94956
ESR1 Protein uniprot:P03372
HSD17B3 Protein uniprot:P37058
SLCO1A2 Protein uniprot:P46721
SLCO4C1 Protein uniprot:Q6ZQN7

References

  1. The sulfatase pathway for estrogen formation: targets for the treatment and diagnosis of hormone-associated tumors. Secky L, Svoboda M, Klameth L, Bajna E, Hamilton G, Zeillinger R, et al. J Drug Deliv. 2013;2013:957605. PubMed Europe PMC Scholia
  2. Clinical significance of the estrogen-modifying enzymes steroid sulfatase and estrogen sulfotransferase in epithelial ovarian cancer. Mungenast F, Aust S, Vergote I, Vanderstichele A, Sehouli J, Braicu E, et al. Oncol Lett. 2017 Jun;13(6):4047–54. PubMed Europe PMC Scholia