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Journal Articles Cancers Year : 2023

Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents


Recent reports suggested a role for microtubules in double-strand-DNA break repair. We herein investigated the role of the microtubule-associated protein Tau in radio- and chemotherapy. Noticeably, a lowered expression of Tau in breast cancer cell lines resulted in a significant decrease in mouse-xenograft breast tumor volume after doxorubicin or X-ray treatments. Furthermore, the knockdown of Tau impaired the classical nonhomologous end-joining pathway and led to an improved cellular response to both bleomycin and X-rays. Investigating the mechanism of Tau’s protective effect, we found that one of the main mediators of response to double-stranded breaks in DNA, the tumor suppressor p53-binding protein 1 (53BP1), is sequestered in the cytoplasm as a consequence of Tau downregulation. We demonstrated that Tau allows 53BP1 to translocate to the nucleus in response to DNA damage by chaperoning microtubule protein trafficking. Moreover, Tau knockdown chemo-sensitized cancer cells to drugs forming DNA adducts, such as cisplatin and oxaliplatin, and further suggested a general role of Tau in regulating the nuclear trafficking of DNA repair proteins. Altogether, these results suggest that Tau expression in cancer cells may be of interest as a molecular marker for response to DNA-damaging anti-cancer agents. Clinically targeting Tau could sensitize tumors to DNA-damaging treatments.
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Dates and versions

inserm-03985380 , version 1 (13-02-2023)



Thomas Rico, Marine Denecha, Raphaelle Caillierez, Thomas Comptdaer, Eric Adriaenssens, et al.. Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents. Cancers, 2023, 15 (1), pp.116. ⟨10.3390/cancers15010116⟩. ⟨inserm-03985380⟩
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