Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2019; 9(13):3952-3965. doi:10.7150/thno.30814 This issue Cite

Research Paper

Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome

Dapeng Hao1*, Jingjing Li1*, Jianlin Wang1, Yuan Meng1, Zhiqiang Zhao1, Chao Zhang1, Kai Miao1, Chuxia Deng1, Benjamin K. Tsang3, Li Wang1,2✉, Li-jun Di1✉

1. Cancer Center, Faculty of health Sciences, University of Macau, Macau, SAR of the People's Republic of China
2. Metabolism Core, Faculty of Health Sciences, University of Macau, Macau, SAR of the People's Republic of China
3. Department of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada
* Equal contribution

✉ Corresponding authors: Di li-jun at lijundiedu.mo and liwangedu.mo. Room 4009, Faculty of Health Sciences (E12), University of Macau, Avenida da Universidade, Taipa, Macau, China. Tel. 853-88224497; Fax. 853-88222314

Citation:
Hao D, Li J, Wang J, Meng Y, Zhao Z, Zhang C, Miao K, Deng C, Tsang BK, Wang L, Di Lj. Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome. Theranostics 2019; 9(13):3952-3965. doi:10.7150/thno.30814. https://www.thno.org/v09p3952.htm
Other styles

File import instruction

Abstract

Graphic abstract

Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers, especially the epithelial ovarian cancer (EOC) which shows defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown.

Methods: We analyzed the estrogen receptor α (ERα) binding profile in EOC cell lines and investigated its association with genome instability, HRR deficiency and sensitivity to chemotherapy using extensive public datasets and in vitro/in vivo experiments.

Results: We found an inverse correlation between estrogen signaling and HRR activity in EOC, and the genome-wide collaboration between ERα and the co-repressor CtBP. Though the non-classical AP-1-mediated ERα signaling, their targets were highly enriched by HRR genes. We found that depleting ERα in EOC cells up-regulates HRR activity and HRR gene expression. Consequently, estrogen signaling enhances the sensitivity of ovarian cancer cells to chemotherapy agents in vitro and in vivo. Large-scale analyses further indicate that estrogen replacement and ESR1 expression are associated with chemo-sensitivity and the favorable survival of EOC patients.

Conclusion: These findings characterize a novel role of ERα in mediating the molecular connection between hormone and HRR in EOC and encourage hormone replacement therapy for EOC patients.

Keywords: Ovarian cancer, Estrogen signaling, Deficiency of homologous-recombination, Chemotherapy, Hormone replacement

Citation styles

APA
Hao, D., Li, J., Wang, J., Meng, Y., Zhao, Z., Zhang, C., Miao, K., Deng, C., Tsang, B.K., Wang, L., Di, L.j. (2019). Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome. Theranostics, 9(13), 3952-3965. https://doi.org/10.7150/thno.30814.

ACS
Hao, D.; Li, J.; Wang, J.; Meng, Y.; Zhao, Z.; Zhang, C.; Miao, K.; Deng, C.; Tsang, B.K.; Wang, L.; Di, L.j. Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome. Theranostics 2019, 9 (13), 3952-3965. DOI: 10.7150/thno.30814.

NLM
Hao D, Li J, Wang J, Meng Y, Zhao Z, Zhang C, Miao K, Deng C, Tsang BK, Wang L, Di Lj. Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome. Theranostics 2019; 9(13):3952-3965. doi:10.7150/thno.30814. https://www.thno.org/v09p3952.htm

CSE
Hao D, Li J, Wang J, Meng Y, Zhao Z, Zhang C, Miao K, Deng C, Tsang BK, Wang L, Di Lj. 2019. Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome. Theranostics. 9(13):3952-3965.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use