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<p>Pancreatic ductal adenocarcinoma (PDAC) is the 3<sup>rd</sup> leading cause of cancer mortality in the U.S., where more than 80% of the cases are diagnosed with metastatic PDAC (mPDAC). In this study, Maeda <i>et al.</i> utilized a CRISPR screen in human patient-derived xenografts from primary and lung metastatic tumors and identified the transcription factor KLF5 as an upstream modulator regulating the mPDAC phenotype. Using a combination of biochemical and molecular experiments together with single-cell genome-wide assays, the authors discovered that KLF5 induces epigenetic modifiers including <i>NCAPD2</i> and <i>MTHFD1</i>, which in turn regulate the expression of a distinct gene profiles controlling the biology of mPDAC. Altogether, the authors defined a cascade of events acting as a domino effect triggered by KLF5, modifying the epigenetic landscape in mPDAC to support metastatic growth. </p>

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A KLF5’s domino effect drives metastatic pancreatic cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月24日

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  • Nicole M. Pena Ruiz,
  • Martin E. Fernandez-Zapico

摘要

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer mortality in the U.S., where more than 80% of the cases are diagnosed with metastatic PDAC (mPDAC). In this study, Maeda et al. utilized a CRISPR screen in human patient-derived xenografts from primary and lung metastatic tumors and identified the transcription factor KLF5 as an upstream modulator regulating the mPDAC phenotype. Using a combination of biochemical and molecular experiments together with single-cell genome-wide assays, the authors discovered that KLF5 induces epigenetic modifiers including NCAPD2 and MTHFD1, which in turn regulate the expression of a distinct gene profiles controlling the biology of mPDAC. Altogether, the authors defined a cascade of events acting as a domino effect triggered by KLF5, modifying the epigenetic landscape in mPDAC to support metastatic growth.