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PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological cancers in Western countries. High-Grade Serous Ovarian Carcinoma (HGSOC) accounts for 60–70% of EOC and is the most aggressive subtype. Reduced PTPN13 expression levels have been previously correlated with worse progno...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607604/ https://www.ncbi.nlm.nih.gov/pubmed/37895093 http://dx.doi.org/10.3390/ijms242015413 |
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author | Aptecar, Leticia Puech, Carole Lopez-Crapez, Evelyne Peter, Marion Coopman, Peter D’Hondt, Véronique Freiss, Gilles |
author_facet | Aptecar, Leticia Puech, Carole Lopez-Crapez, Evelyne Peter, Marion Coopman, Peter D’Hondt, Véronique Freiss, Gilles |
author_sort | Aptecar, Leticia |
collection | PubMed |
description | Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological cancers in Western countries. High-Grade Serous Ovarian Carcinoma (HGSOC) accounts for 60–70% of EOC and is the most aggressive subtype. Reduced PTPN13 expression levels have been previously correlated with worse prognosis in HGSOC. However, PTPN13’s exact role and mechanism of action in these tumors remained to be investigated. To elucidate PTPN13’s role in HGSOC aggressiveness, we used isogenic PTPN13-overexpressing clones of the OVCAR-8 cell line, which poorly expresses PTPN13, and also PTPN13 CRISPR/Cas9-mediated knockout/knockdown clones of the KURAMOCHI cell line, which strongly expresses PTPN13. We investigated their migratory and invasive capacity using a wound healing assay, their mesenchymal-epithelial transition (EMT) status using microscopy and RT-qPCR, and their sensitivity to chemotherapeutic drugs used for HGSOC. We found that (i) PTPN13 knockout/knockdown increased migration and invasion in KURAMOCHI cells that also displayed a more mesenchymal phenotype and increased expression of the SLUG, SNAIL, ZEB-1, and ZEB-2 EMT master genes; and (ii) PTPN13 expression increased the platinum sensitivity of HGSOC cells. These results suggest that PTPN13 might be a predictive marker of response to platinum salts in HGSOC. |
format | Online Article Text |
id | pubmed-10607604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106076042023-10-28 PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells Aptecar, Leticia Puech, Carole Lopez-Crapez, Evelyne Peter, Marion Coopman, Peter D’Hondt, Véronique Freiss, Gilles Int J Mol Sci Article Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological cancers in Western countries. High-Grade Serous Ovarian Carcinoma (HGSOC) accounts for 60–70% of EOC and is the most aggressive subtype. Reduced PTPN13 expression levels have been previously correlated with worse prognosis in HGSOC. However, PTPN13’s exact role and mechanism of action in these tumors remained to be investigated. To elucidate PTPN13’s role in HGSOC aggressiveness, we used isogenic PTPN13-overexpressing clones of the OVCAR-8 cell line, which poorly expresses PTPN13, and also PTPN13 CRISPR/Cas9-mediated knockout/knockdown clones of the KURAMOCHI cell line, which strongly expresses PTPN13. We investigated their migratory and invasive capacity using a wound healing assay, their mesenchymal-epithelial transition (EMT) status using microscopy and RT-qPCR, and their sensitivity to chemotherapeutic drugs used for HGSOC. We found that (i) PTPN13 knockout/knockdown increased migration and invasion in KURAMOCHI cells that also displayed a more mesenchymal phenotype and increased expression of the SLUG, SNAIL, ZEB-1, and ZEB-2 EMT master genes; and (ii) PTPN13 expression increased the platinum sensitivity of HGSOC cells. These results suggest that PTPN13 might be a predictive marker of response to platinum salts in HGSOC. MDPI 2023-10-21 /pmc/articles/PMC10607604/ /pubmed/37895093 http://dx.doi.org/10.3390/ijms242015413 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Aptecar, Leticia Puech, Carole Lopez-Crapez, Evelyne Peter, Marion Coopman, Peter D’Hondt, Véronique Freiss, Gilles PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title | PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title_full | PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title_fullStr | PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title_full_unstemmed | PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title_short | PTPN13 Participates in the Regulation of Epithelial–Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells |
title_sort | ptpn13 participates in the regulation of epithelial–mesenchymal transition and platinum sensitivity in high-grade serous ovarian carcinoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607604/ https://www.ncbi.nlm.nih.gov/pubmed/37895093 http://dx.doi.org/10.3390/ijms242015413 |
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