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Updated: Jul 13, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation

Chi-Hwa Wu1, Jan van Riggelen, Alper Yetil

  • 1Department of Medicine, Division of Oncology, Stanford University School of Medicine, CA 94305, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 1, 2007
PubMed

Insights

Suppressing the c-Myc (MYC) oncogene triggers cellular senescence, a tumor-suppressing mechanism, in various cancers. This reactivation of senescence programs offers a critical therapeutic vulnerability in established tumors.

Area of Science:

  • Oncology
  • Cellular Biology
  • Cancer Research

Background:

  • Oncogene-induced senescence is a crucial barrier against cancer development.
  • The role of c-Myc (MYC) in driving senescence across diverse tumor types remains incompletely understood.

Purpose of the Study:

  • To investigate the impact of c-Myc (MYC) oncogene suppression on cellular senescence in established tumors.
  • To identify the molecular mechanisms and genetic dependencies underlying MYC-induced senescence.

Main Methods:

  • Analysis of senescence markers (e.g., acidic beta-gal staining, p16INK4a, p15INK4b expression) following MYC inactivation in lymphoma, osteosarcoma, and hepatocellular carcinoma models.
  • Chromatin structure analysis, including histone H4 acetylation and histone H3 K9 methylation.
  • Assessment of senescence and tumor regression in genetically modified osteosarcoma and lymphoma models with altered p16INK4a, Rb, or p53 pathways.
  • Evaluation of the effect of pharmacologic inhibitors of ATM/ATR and MAPK signaling pathways.

Main Results:

  • MYC inactivation induced senescence markers and altered chromatin structure (reduced H4 acetylation, increased H3 K9 methylation) in diverse tumor types.
  • Senescence induction and sustained tumor regression upon MYC inactivation were dependent on p16INK4a/Rb in osteosarcomas and p53 in lymphomas.
  • Pharmacologic inhibition of ATM/ATR and MAPK pathways did not impede MYC-driven senescence.

Conclusions:

  • Cellular senescence programs are latently functional in established tumors and can be reactivated by MYC inactivation.
  • MYC inactivation-induced senescence represents a critical mechanism of oncogene addiction, offering a potential therapeutic strategy.

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