Related Experiment Video

Updated: Jan 13, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

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KMT2C inactivation leads to PTEN downregulation and tolerance to DNA damage during cell cycle progression

Theodoros Rampias1, Andreas Goutas2, Dimitris Karagiannis2

  • 1Biomedical Research Foundation Academy of Athens, Athens, Greece. trampias@bioacademy.gr.

NPJ Precision Oncology
|October 29, 2025
PubMed

Insights

Loss of KMT2C protein, a cancer hallmark, drives tumor growth and DNA damage tolerance. Targeting mitotic progression with PLK1 inhibitors shows promise for treating KMT2C-deficient solid tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Cancer is characterized by uncontrolled proliferation, apoptosis resistance, genomic instability, and epigenetic reprogramming.
  • Deregulation of gene expression and signaling networks underlies these interconnected cancer hallmarks.
  • KMT2C is frequently mutated in solid malignancies and its role in cancer progression is under investigation.

Purpose of the Study:

  • To investigate the role of KMT2C in cancer development and progression.
  • To identify potential therapeutic strategies for KMT2C-deficient tumors.

Main Methods:

  • Analysis of patient data and cellular models.
  • Investigation of KMT2C's impact on oncogenic signaling pathways (PI3K/AKT).
  • Assessment of DNA damage response and cell cycle progression.
  • In vivo efficacy studies using a PLK1 inhibitor.

Main Results:

  • KMT2C loss is a poor prognostic marker in bladder cancer.
  • KMT2C deficiency activates the PI3K/AKT pathway, promoting proliferation and apoptosis resistance.
  • KMT2C-deficient cells exhibit tolerance to DNA damage but are sensitive to mitotic stress.
  • PLK1 inhibition effectively reduced tumor growth in vivo, inducing mitotic catastrophe and senescence.

Conclusions:

  • KMT2C plays a critical role in maintaining cancer cell viability and genome integrity.
  • Targeting mitotic progression, specifically with PLK1 inhibitors, represents a promising therapeutic strategy for KMT2C-loss solid tumors.

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