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Updated: Aug 15, 2025
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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
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Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents
Thomas Rico1, Marine Denechaud1, Raphaelle Caillierez1
1Alzheimer & Tauopathies, UMR-S1172, Lille Neuroscience & Cognition, CHU-Lille, Inserm, Univ. Lille, F-59000 Lille, France.
Cancers
|January 8, 2023
Summary
The microtubule-associated protein Tau protects cancer cells from DNA damage. Lowering Tau levels enhances chemotherapy and radiation effectiveness by improving DNA repair protein nuclear transport, suggesting Tau as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Microtubules are implicated in DNA double-strand break repair.
- The role of microtubule-associated protein Tau in cancer treatment response is underexplored.
Purpose of the Study:
- To investigate the role of Tau in radio- and chemotherapy response.
- To elucidate the mechanism by which Tau influences DNA damage repair.
Main Methods:
- Breast cancer cell lines and mouse xenografts were used.
- Tau expression was modulated (lowered/knocked down).
- DNA repair pathways (nonhomologous end-joining) and protein trafficking (53BP1 nuclear translocation) were analyzed.
Main Results:
- Reduced Tau expression significantly decreased tumor volume post-treatment with doxorubicin or X-rays.
- Tau knockdown impaired nonhomologous end-joining and sensitized cells to DNA-damaging agents (bleomycin, X-rays, cisplatin, oxaliplatin).
- Tau downregulation caused cytoplasmic sequestration of 53BP1, a key DNA damage response protein.
Conclusions:
- Tau facilitates 53BP1 nuclear translocation for DNA repair.
- Tau expression may serve as a predictive marker for response to DNA-damaging anti-cancer agents.
- Targeting Tau could sensitize tumors to conventional chemoradiotherapy.
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