ATM Modulates Nuclear Mechanics by Regulating Lamin A Levels
Pragya Shah1, Connor W McGuigan1, Svea Cheng1
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, United States.
Frontiers in Cell and Developmental Biology
|June 20, 2022
Summary
Ataxia-telangiectasia mutated (ATM) kinase inhibition reduces lamin A, increasing nuclear deformability and cell migration. This ATM-lamin A link may enhance cancer cell metastasis.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Ataxia-telangiectasia mutated (ATM) is a key kinase in DNA damage response.
- Emerging roles for ATM include regulation of oxidative stress and metabolism.
- ATM mutations are linked to Ataxia Telangiectasia and various cancers.
Purpose of the Study:
- To investigate novel functions of ATM beyond DNA repair.
- To explore the impact of ATM inhibition or deletion on cellular mechanics.
- To identify potential therapeutic targets for ATM-mutated cancers.
Main Methods:
- Utilized ATM inhibition and gene deletion models.
- Assessed expression levels of nuclear envelope proteins, specifically lamin A.
- Measured nuclear deformability and cell migration through confined environments.
Main Results:
- ATM inhibition and deletion significantly reduced lamin A expression.
- ATM-deficient cells exhibited increased nuclear deformability.
- Enhanced cell migration through restrictive spaces was observed in ATM-inhibited/deleted cells.
Conclusions:
- A novel link between ATM and lamin A expression was discovered.
- ATM regulates nuclear stiffness and cell migration via lamin A.
- This finding has implications for understanding and treating ATM-mutated cancers, potentially impacting metastatic potential.
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