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ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation

Huiting Deng1,2, Hailin Liu3, Guoyue Yang1

  • 1Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai University, 83 Jintang Road, Tianjin, 300170, People's Republic of China.

Oncogenesis
|March 29, 2023
PubMed

Insights

Researchers identified Olig2 as a key driver of lung cancer stemness, regulating CD133. The drug ACT001 targets Olig2, showing potential for effective lung cancer stem cell therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Lung cancer remains a leading cause of cancer mortality with limited therapeutic advancements.
  • Lung cancer stem cells (LCSCs) are implicated in tumor progression, recurrence, and drug resistance.
  • Targeting LCSCs is crucial for developing effective lung cancer treatments.

Purpose of the Study:

  • To investigate the role of Olig2 in lung cancer stemness.
  • To identify Olig2 as a potential therapeutic target for eliminating LCSCs.
  • To evaluate the efficacy of ACT001 in targeting Olig2 and LCSCs.

Main Methods:

  • Analysis of Olig2 expression in clinical lung cancer tissues.
  • Investigated Olig2's role as a transcription factor regulating CD133.
  • Assessed ACT001's mechanism of action, including protein binding and degradation of Olig2.

Main Results:

  • Olig2 was found to be overexpressed in lung cancer tissues.
  • Olig2 regulates cancer stemness by controlling CD133 gene transcription.
  • ACT001 directly binds to Olig2, promoting its degradation and inhibiting CD133 transcription, thereby reducing cancer stemness.

Conclusions:

  • Olig2 is a promising druggable target for anti-LCSC therapy.
  • ACT001 demonstrates potential as a therapeutic agent for lung cancer by targeting Olig2.
  • These findings support the clinical application of ACT001 in lung cancer treatment.

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