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<p>Ovarian cancer is characterized by aggressive metastasis, chemoresistance, and poor survival outcomes. Gaps in understanding of factors that drive these phenotypes have hindered the development of actionable therapeutic targets. We demonstrate that Zinc Finger Protein 217 (ZNF217) is a key pro-metastatic factor in ovarian cancer cells. ZNF217 overexpression dramatically increases proliferation, metastasis, and chemoresistance while its depletion impairs these phenotypes. Consistently, ZNF217 overexpression is associated with poor prognosis in both mouse models and ovarian cancer patients. Interestingly, ZNF217 induces metastatic phenotypes in fallopian tube cells, suggesting potential role in the transition of early-stage tumors to aggressive carcinoma. ZNF217’s oncogenic activity is dependent on its ability to bind DNA and alter multiple processes, including EMT, that are critical in driving different aspects of cancer progression. Thus, our data establishes ZNF217 as a potent oncogene in ovarian cancer cells that impacts multiple steps in the metastatic process and a potential therapeutic target.</p>

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ZNF217 promotes ovarian cancer progression by impacting multiple pivotal steps in the metastatic process

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月4日

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  • Kathryn C. Wardrup,
  • Jessica Hoffman,
  • Megha J. Pandya,
  • Nithya Navarathna,
  • Mohan E. Tulapurkar,
  • Achuth Padmanabhan

摘要

Ovarian cancer is characterized by aggressive metastasis, chemoresistance, and poor survival outcomes. Gaps in understanding of factors that drive these phenotypes have hindered the development of actionable therapeutic targets. We demonstrate that Zinc Finger Protein 217 (ZNF217) is a key pro-metastatic factor in ovarian cancer cells. ZNF217 overexpression dramatically increases proliferation, metastasis, and chemoresistance while its depletion impairs these phenotypes. Consistently, ZNF217 overexpression is associated with poor prognosis in both mouse models and ovarian cancer patients. Interestingly, ZNF217 induces metastatic phenotypes in fallopian tube cells, suggesting potential role in the transition of early-stage tumors to aggressive carcinoma. ZNF217’s oncogenic activity is dependent on its ability to bind DNA and alter multiple processes, including EMT, that are critical in driving different aspects of cancer progression. Thus, our data establishes ZNF217 as a potent oncogene in ovarian cancer cells that impacts multiple steps in the metastatic process and a potential therapeutic target.