2. Academic Validation
  3. A Novel Estrogen Receptor β Agonist Diminishes Ovarian Cancer Stem Cells via Suppressing the Epithelial-to-Mesenchymal Transition

A Novel Estrogen Receptor β Agonist Diminishes Ovarian Cancer Stem Cells via Suppressing the Epithelial-to-Mesenchymal Transition

  • Cancers (Basel). 2022 May 6;14(9):2311. doi: 10.3390/cancers14092311.
Ananya Banerjee 1 2,  Shurui Cai 1 2,  Guozhen Xie 2,  Na Li 1 2,  Xuetao Bai 1 2,  Kousalya Lavudi 1 2,  Kevin Wang 3,  Xiaoli Zhang 4,  Junran Zhang 1 2,  Srinivas Patnaik 5,  Floor J Backes 6,  Chad Bennett 7,  Qi-En Wang 1 2
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • 2 Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • 3 Columbus Academy, Gahanna, OH 43230, USA.
  • 4 Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • 5 School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar 751024, India.
  • 6 Division of Gynecologic Oncology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • 7 Drug Development Institute, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
PMID: 35565440 DOI: 10.3390/cancers14092311
Abstract

Epithelial ovarian Cancer is the most lethal malignancy of the female reproductive tract. A healthy ovary expresses both Estrogen Receptor α (ERα) and β (ERβ). Given that ERα is generally considered to promote cell survival and proliferation, thereby, enhancing tumor growth, while ERβ shows a protective effect against the development and progression of tumors, the activation of ERβ by its agonists could be therapeutically beneficial for ovarian Cancer. Here, we demonstrate that the activation of ERβ using a newly developed ERβ Agonist, OSU-ERb-12, can impede ovarian Cancer cell expansion and tumor growth in an ERα-independent manner. More interestingly, we found that OSU-ERb-12 also reduces the Cancer stem cell (CSC) population in ovarian Cancer by compromising non-CSC-to-CSC conversion. Mechanistically, we revealed that OSU-ERb-12 decreased the expression of Snail, a master regulator of the epithelial-to-mesenchymal transition (EMT), which is associated with de novo CSC generation. Given that ERα can mediate EMT and facilitate maintenance of the CSC subpopulation and that OSU-ERb-12 can block the transactivity of ERα, we conclude that OSU-ERb-12 reduces the CSC subpopulation by inhibiting EMT in an ERα-dependent manner. Taken together, our data indicate that the ERβ Agonist OSU-ERb-12 could be used to hinder tumor progression and limit the CSC subpopulation with the potential to prevent tumor relapse and metastasis in patients with ovarian Cancer.

Keywords

Estrogen receptor; cancer stem cells; epithelial-to-mesenchymal transition; ovarian cancer.

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