Implication of Ataxia-Telangiectasia-mutated kinase in epithelium-mesenchyme transition

Tianyu Miao1, Changsheng Peng2, Zizhi Tang2

  • 1Vascular Surgery of West China Hospital, Sichuan University, Chengdu, PR China.

Carcinogenesis
|January 8, 2021
PubMed

Insights

DNA damage activates ATM kinase, promoting cancer cell migration and metastasis by inducing epithelial-mesenchyme transition (EMT). Inhibiting ATM reduces this procancer effect, highlighting its role in cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cancer development is linked to genome instability and disrupted anti-cancer barriers.
  • DNA damage response factors, like ATM kinase, are vital for maintaining genomic integrity and initiating cell death.
  • Cytotoxic therapies, while targeting cancer, can paradoxically promote metastasis through poorly understood mechanisms.

Purpose of the Study:

  • To investigate the mechanisms by which cytotoxic therapies may promote cancer metastasis.
  • To explore the role of DNA damage response pathways, specifically ATM kinase, in mediating the pro-metastatic effects of cancer treatments.
  • To identify potential therapeutic targets for preventing cancer cell migration and metastasis.

Main Methods:

  • Analyzing gene expression changes in cancer cells following cytotoxic treatment.
  • Utilizing chemical inhibitors to assess the role of ATM kinase in DNA damage-induced cellular responses.
  • Evaluating cell mobility and epithelial-mesenchyme transition (EMT) markers.
  • Examining ATM activation and metastatic potential in clinical ovarian cancer tissues.

Main Results:

  • Cytotoxic treatments induce significant alterations in EMT-related gene expression in cancer cells.
  • DNA damage strongly stimulates EMT-dependent cancer cell mobility.
  • ATM kinase activity is essential for the induction of EMT and enhanced cell mobility upon DNA damage.
  • ATM activation in cancer cells correlates with increased metastatic potential in ovarian cancer tissues.

Conclusions:

  • ATM kinase plays a critical role in promoting cancer cell metastasis by driving EMT gene expression.
  • Targeting ATM kinase may represent a novel therapeutic strategy to inhibit cancer cell migration and prevent metastasis.
  • Understanding the dual role of cytotoxic therapy in cancer treatment is crucial for developing effective anti-cancer strategies.

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