Scholarlink

<p>Ovarian cancer remains a deadly gynecological malignancy, with <i>PTEN</i> loss and <i>TP53</i> mutations frequently implicated in its progression. However, suitable models for studying ovarian cancers with <i>PTEN</i> and <i>TP53</i> deletions are rare. Here we develop and validate the mouse ovarian epithelium with <i>Pten</i> and <i>Trp53</i> deletions (MEPP) model using the EPI-SauriCas9 system. We demonstrate the role of <i>Pten</i> loss in promoting tumorigenicity and metastasis. Single-cell RNA sequencing reveals distinct epithelial subpopulations with varying metastatic potential. MEPP also recapitulates key features of human ovarian cancer, including its immune landscape and therapeutic responses. High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in <i>PTEN</i>-deleted organoids. Together, these results establish MEPP as a platform for studying <i>PTEN-</i>deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月29日

查看全文
  • Wutao Chen,
  • Pengju He,
  • Ling Ding,
  • Weihua Lou,
  • Yishu Wang,
  • Weiwei Shi,
  • Zhangzhengyi Fan,
  • Yumeng Sheng,
  • Jing Luo,
  • Zhixing Tan,
  • You Wang,
  • Wen Di,
  • Xiaoping Ke,
  • Bin Yu

摘要

Ovarian cancer remains a deadly gynecological malignancy, with PTEN loss and TP53 mutations frequently implicated in its progression. However, suitable models for studying ovarian cancers with PTEN and TP53 deletions are rare. Here we develop and validate the mouse ovarian epithelium with Pten and Trp53 deletions (MEPP) model using the EPI-SauriCas9 system. We demonstrate the role of Pten loss in promoting tumorigenicity and metastasis. Single-cell RNA sequencing reveals distinct epithelial subpopulations with varying metastatic potential. MEPP also recapitulates key features of human ovarian cancer, including its immune landscape and therapeutic responses. High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.