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Updated: Nov 22, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
Impairment of genome instability drives the development of cancer by disrupting anti-cancer barriers. Upon genotoxic insults, DNA damage responsive factors, notably ATM kinase, is crucial to protect genomic integrity while promoting cell death. Meanwhile, cytotoxic therapy-inducing DNA lesions is double-edged sword by causing cancer metastasis based on animal models and clinical observations. The underlying mechanisms for the procancer effect of cytotoxic therapies are poorly understood. Here, we report that cancer cells subjected to cytotoxic treatments elicit dramatic alteration of gene expression controlling the potential of epithelium-mesenchyme transition (EMT). Resultantly, EMT-dependent cell mobility is potently induced upon DNA damage. This stimulation of EMT is mainly Ataxia-Telangiectasia-mutated (ATM)-dependent, as the chemical inhibitor specifically inhibiting ATM kinase activity can suppress the EMT gene expression and thus cell mobility. At last, we show that cancer cells with ATM activation display increased metastatic potential in ovarian cancer tissues. Taken together, we reveal a novel role of ATM in promoting metastatic potential of cancer cells by favoring EMT gene expression.
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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