Sulfatase and aromatase pathway (Homo sapiens)

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The sulfatase pathway plays an essential role in estrogen-related breast and endometrial cancer by enabling the production of E2 within tumors using circulating E1S. This pathway involves two crucial enzymes: STS, which activates estrogen, and SULT1E1, which deactivates estrogen. Research indicates that increased STS expression and E2 production are associated with the progression of breast and ovarian cancer. However, the sulfonation of E2 through SULT1E1 reduces the proliferative effects of estrogens on hormone-sensitive tumor cells. Additionally, the conjugation of estrogens by SULT1E1 generates water-soluble estrogen sulfates that can be efficiently excreted from cells. This effective sulfonation and rapid excretion of sulfonated E2 help prevent the metabolic activation of the hormone into potentially harmful catechol metabolites. Consequently, targeting the sulfatase pathway could be a promising therapeutic approach for certain patients with estrogen-responsive EOC.

This pathway is based on: 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

and: 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;2013:957605. doi: 10.1155/2013/957605. Epub 2013 Feb 13. PMID: 23476785; PMCID: PMC3586502.