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Updated: Dec 1, 2025
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Live-imaging of Breast Epithelial Cell Migration After the Transient Depletion of TIP60
Published on: December 7, 2017
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Nuclear Localization Is Not Required for Tip60 Tumor Suppressor Activity in Breast and Lung Cancer Cells
Priyadarshini Ravichandran1, Simon A Davis2, Himali Vashishtha3
1Feinstein Institute for Medical Research, Manhasset, New York, USA.
DNA and Cell Biology
|November 6, 2020
Summary
Tip60 (lysine acetyltransferase) shifts to the cytoplasm in breast and lung cancer cells, suggesting altered subcellular localization contributes to cancer development. This Tip60 dysregulation impacts cancer cell sensitivity to paclitaxel.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tip60 is a lysine acetyltransferase with dual roles as a tumor suppressor and oncogene depending on cancer type.
- Tip60 typically localizes to the nucleus, regulating transcription, DNA repair, and chromatin.
- Cytoplasmic acetylation by Tip60 has also been observed.
Purpose of the Study:
- To investigate the relationship between Tip60 subcellular localization and breast and lung cancer.
- To determine if Tip60 localization patterns differ between normal and cancer cells.
Main Methods:
- Cell fractionation experiments to assess endogenous Tip60 distribution.
- Immunofluorescence microscopy to visualize overexpressed Tip60 localization patterns.
- Manipulation of nuclear localization signals (NLS) to alter Tip60 localization.
Main Results:
- Cancer-derived cell lines exhibited a shift in endogenous Tip60 from nuclear to cytoplasmic localization compared to normal cell lines.
- Overexpressed Tip60 showed increased cytoplasmic localization in cancer cells versus HEK-293 cells.
- Tip60 overexpression enhanced cancer cell sensitivity to paclitaxel, irrespective of its subcellular localization.
Conclusions:
- Tip60 dysregulation in breast and lung cancer involves altered subcellular localization, not solely reduced expression.
- Changes in Tip60 localization may play a role in cancer progression and treatment response.
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