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Updated: Jun 6, 2025

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Inhibition of lung tumorigenesis by transient reprogramming in cancer cells

Pablo Pedrosa1, Zhenguang Zhang2, Victor Nuñez-Quintela2

  • 1Cell Senescence, Cancer and Aging Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.

Cell Death & Disease
|November 25, 2024
PubMed

Insights

Transient expression of reprogramming factors (Oct4, Sox2, Klf4, c-Myc) induces apoptosis and senescence in lung cancer cells, impairing tumor growth. This suggests a novel therapeutic strategy for oncology.

Area of Science:

  • Oncology
  • Cellular reprogramming
  • Cancer biology

Background:

  • Oncogenic transformation and induced pluripotency are distinct cellular fates.
  • The effect of transient reprogramming factor expression in cancer cells is not well understood.

Purpose of the Study:

  • To investigate the impact of transient expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) on cancer cells.
  • To elucidate the mechanisms by which OSKM affects tumor growth.
  • To evaluate the therapeutic potential of transient reprogramming in vivo.

Main Methods:

  • Expression of OSKM in transformed lung cells and cancer cell lines.
  • Assessment of apoptosis and senescence induction.
  • Identification of key reprogramming factors and downstream mediators (p21).
  • In vivo studies using allografts, orthotopic transplantation, and KRAS-driven lung cancer mouse models.

Main Results:

  • Transient OSKM expression limits transformed lung cell growth by inducing apoptosis and senescence.
  • Oct4 and Klf4 were identified as the primary factors responsible for this antitumorigenic effect.
  • The cell cycle inhibitor p21 mediates OSKM-induced cell death and senescence.
  • In vivo models demonstrated that transient reprogramming impairs tumor growth and reduces tumor burden.

Conclusions:

  • Transient induction of reprogramming factors in cancer cells has an antitumorigenic effect.
  • This approach offers a novel therapeutic strategy for cancer treatment.

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