PDF(Pubmed)
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.
摘要：
上皮性卵巢癌（EOC）是西方国家妇科癌症死亡的主要原因。高级别浆液性卵巢癌（HGSOC）占EOC的60-70％，是最具侵袭性的亚型。PTPN13表达水平的降低先前已与HGSOC的不良预后相关。然而,PTPN13在这些肿瘤中的确切作用和作用机制仍有待研究。为了阐明PTPN13在HGSOC攻击性中的作用，我们使用了OVCAR-8细胞系的等基因PTPN13过表达的克隆，低表达PTPN13，以及PTPN13CRISPR/Cas9介导的KURAMOCHI细胞系的敲除/敲低克隆，强烈表达PTPN13。我们使用伤口愈合试验研究了它们的迁移和侵入能力，使用显微镜和RT-qPCR，它们的间充质-上皮转化（EMT）状态，以及它们对用于HGSOC的化疗药物的敏感性。我们发现（i）PTPN13敲除/敲除增加KURAMOCHI细胞的迁移和侵袭，这也显示出更多的间充质表型和SLUG的表达增加，蜗牛,ZEB-1和ZEB-2EMT主基因;和(ii)PTPN13表达增加HGSOC细胞的铂敏感性。这些结果表明PTPN13可能是HGSOC中响应铂盐的预测标记。
