Affiliation:
1. IRCM (Institut de Recherche en Cancérologie de Montpellier), University of Montpellier, Inserm, ICM (Institut du Cancer de Montpellier), F-34000 Montpellier, France
2. CNRS—Centre National de la Recherche Scientifique, 1919 Route de Mende, F-34293 Montpellier, France
Abstract
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.
Funder
Ligue Nationale Contre le Cancer
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
3 articles.
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