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<p>To elucidate the complex interplay of undifferentiated cancer cells in malignancy, we focus on the crucial mechanisms that maintain the undifferentiated state of cancer stem-like cells, which drive tumor growth and therapy resistance. Here, we identify a protein called dehydrogenase/reductase 13 (DHRS13) that is abundant in undifferentiated glioblastoma cells. DHRS13 is primarily located in the mitochondria and functions as a retinaldehyde reductase, converting all-<i>trans</i>-retinaldehyde to all-<i>trans</i>-retinol with high affinity for NADPH. Mechanistically, DHRS13 prevents glioma stem-like cells from differentiating by blocking retinoic acid signaling, thereby maintaining their undifferentiated state. Remarkably, the depletion of DHRS13 results in mitochondrial reactive oxygen species-driven mitophagy and cell death. Consequently, loss of DHRS13 leads to a significant decrease in tumor initiation and progression. These findings hold promise for the development of strategies that target undifferentiated cancer cells, potentially leading to improved treatment outcomes.</p>

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DHRS13 suppresses differentiation and mitophagy in glioma via retinoic acid and mitochondrial reactive oxygen species

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月30日

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  • Sunyoung Seo,
  • Min Ji Park,
  • Min Gi Park,
  • Minseo Gwak,
  • Yoonji Kim,
  • Junseok Jang,
  • Nayoung Hong,
  • Bok-Sim Lee,
  • Chohee Kim,
  • Seonguk Jo,
  • Hyun Bo Shim,
  • Hyun-Jin Kim,
  • Myung Hun Kim,
  • Seo Hyun Yoo,
  • Seunghyun Yoon,
  • Sua Kim,
  • Jae Hyuk Lee,
  • Sang-Hun Choi,
  • Seon Yong Lee,
  • Gyu-Bum Yeon,
  • Sung-Hye Park,
  • Sung-Hak Kim,
  • Hyunjeong Lee,
  • Joo-Yong Lee,
  • Dae-Sung Kim,
  • Byung Cheon Lee,
  • Jong-Whi Park,
  • Hyunggee Kim

摘要

To elucidate the complex interplay of undifferentiated cancer cells in malignancy, we focus on the crucial mechanisms that maintain the undifferentiated state of cancer stem-like cells, which drive tumor growth and therapy resistance. Here, we identify a protein called dehydrogenase/reductase 13 (DHRS13) that is abundant in undifferentiated glioblastoma cells. DHRS13 is primarily located in the mitochondria and functions as a retinaldehyde reductase, converting all-trans-retinaldehyde to all-trans-retinol with high affinity for NADPH. Mechanistically, DHRS13 prevents glioma stem-like cells from differentiating by blocking retinoic acid signaling, thereby maintaining their undifferentiated state. Remarkably, the depletion of DHRS13 results in mitochondrial reactive oxygen species-driven mitophagy and cell death. Consequently, loss of DHRS13 leads to a significant decrease in tumor initiation and progression. These findings hold promise for the development of strategies that target undifferentiated cancer cells, potentially leading to improved treatment outcomes.