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Updated: Jul 4, 2026

Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice
Published on: June 30, 2021
ATP modulates PTEN subcellular localization in multiple cancer cell lines.
Glenn P Lobo1, Kristin A Waite, Sarah M Planchon
1Genomic Medicine Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, NE-50, Cleveland, OH 44195, USA.
Adenosine triphosphate (ATP) regulates the location of the tumor suppressor PTEN within cells. Lower ATP levels increase nuclear PTEN, impacting cancer development across various cell types.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The tumor suppressor gene PTEN is crucial in breast cancer development.
- PTEN's role in regulating the PI3K/Akt pathway is known, but its nuclear functions are increasingly recognized.
- Existing mechanisms for PTEN's subcellular localization are not universally applicable across different cell types.
Purpose of the Study:
- To investigate the role of adenosine triphosphate (ATP) in regulating PTEN's subcellular localization.
- To determine if ATP-mediated regulation of PTEN localization is conserved across diverse cancer cell lines.
Main Methods:
- Utilized various cancer cell lines (breast, colon, thyroid).
- Manipulated intracellular ATP levels.
- Assessed PTEN protein levels in the nucleus under different conditions.
Main Results:
- Adenosine triphosphate (ATP) was identified as a regulator of PTEN subcellular localization.
- ATP-deficient cells exhibited increased nuclear PTEN protein.
- Supplementation with ATP, ADP, or AMP reversed the increase in nuclear PTEN.
- Non-hydrolyzable ATP analogue (ATPgammaS) did not consistently reverse nuclear PTEN levels.
Conclusions:
- ATP influences PTEN's location within the cell, affecting its function.
- This ATP-dependent regulation of PTEN localization appears to be a common mechanism across multiple cancer cell lineages.
- Findings suggest a novel, broadly applicable mechanism influencing PTEN's role in carcinogenesis.
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