Cargando…
The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells
BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3’-phospoadenosine 5’-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases D...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486135/ https://www.ncbi.nlm.nih.gov/pubmed/37684671 http://dx.doi.org/10.1186/s13048-023-01262-7 |
_version_ | 1785102940988506112 |
---|---|
author | Sun, Lei Ji, Wei-Xue Li, Yan Li, Ze-Lian Duan, Can-Can Xia, Bai-rong Xiao, Lan |
author_facet | Sun, Lei Ji, Wei-Xue Li, Yan Li, Ze-Lian Duan, Can-Can Xia, Bai-rong Xiao, Lan |
author_sort | Sun, Lei |
collection | PubMed |
description | BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3’-phospoadenosine 5’-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC). RESULTS: Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin. CONCLUSIONS: These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01262-7. |
format | Online Article Text |
id | pubmed-10486135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104861352023-09-09 The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells Sun, Lei Ji, Wei-Xue Li, Yan Li, Ze-Lian Duan, Can-Can Xia, Bai-rong Xiao, Lan J Ovarian Res Research BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3’-phospoadenosine 5’-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC). RESULTS: Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin. CONCLUSIONS: These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01262-7. BioMed Central 2023-09-08 /pmc/articles/PMC10486135/ /pubmed/37684671 http://dx.doi.org/10.1186/s13048-023-01262-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sun, Lei Ji, Wei-Xue Li, Yan Li, Ze-Lian Duan, Can-Can Xia, Bai-rong Xiao, Lan The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title | The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title_full | The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title_fullStr | The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title_full_unstemmed | The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title_short | The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
title_sort | papss1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486135/ https://www.ncbi.nlm.nih.gov/pubmed/37684671 http://dx.doi.org/10.1186/s13048-023-01262-7 |
work_keys_str_mv | AT sunlei thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT jiweixue thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT liyan thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT lizelian thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT duancancan thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT xiabairong thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT xiaolan thepapss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT sunlei papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT jiweixue papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT liyan papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT lizelian papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT duancancan papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT xiabairong papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells AT xiaolan papss1geneisamodulatorofresponsetocisplatinbyregulatingestrogenreceptoralphasignalingactivityinovariancancercells |