From fallopian tube epithelium to high-grade serous ovarian cancer : a single-cell resolution review of sex steroid hormone signaling

Gjorgoska, Marija (author), Lanišnik-Rižner, Tea (author)

High-grade serous ovarian cancer (HGSOC) represents the most lethal subtype of ovarian cancer, largely due to being commonly diagnosed at advanced stages. The early molecular mechanisms underlying ovarian carcinogenesis remain poorly defined, posing challenges to the development of prevention and early detection strategies. Here we dissect the molecular mechanisms of sex steroid hormone signaling throughout the decades-long evolution of HGSOC precursor lesions, which predominantly originate from secretory epithelial cells of fallopian tubes (FT). We also discuss the prognostic significance of sex steroid receptor isoforms and steroid metabolizing enzymes in HGSOCs. Finally, we provide a comprehensive gene expression atlases of sex steroid receptors, steroidogenic, and steroid-metabolizing enzymes across different cell populations in pre- and postmenopausal FTs, and HGSOCs, using published single-cell RNA sequencing datasets. These atlases reveal that secretory epithelial cells and stromal populations in FTs express sex steroid receptors and enzymes responsible for the formation and inactivation of genotoxic estrogen metabolites. In HGSOC, epithelial cells express various HSD17B isoforms and steroid conjugating enzymes, suggesting an enhanced ability to finely regulate the levels of bioactive sex steroids.

• Language: English
• Keywords: androgens, estrogens, high-grade serous ovarian cancer, progestogens, serous tubal intraepithelial carcinoma, sex steroid receptors
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 10 str.
• Numbering: Vol. 96, art. 101302
• PID: 20.500.12556/RUL-165164
• UDC: 577.2
• ISSN on article: 1873-2194
• DOI: 10.1016/j.plipres.2024.101302
• COBISS.SI-ID: 216006659
• Publication date in RUL: 25.11.2024

Record is a part of a journal

• Title: Progress in lipid research
• Publisher: Elsevier
• ISSN: 1873-2194
• COBISS.SI-ID: 175211779

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: androgeni, estrogeni, serozni rak jajčnikov visoke stopnje, progestogeni, receptorji za spolne steroide

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J3-2535
• Name: Vloga androgenov pri hormonsko odvisnih boleznih: pomen za diagnostiko in zdravljenje

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0449
• Name: Translacijska molekularna endokrinologija za zdravje žensk