Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents

Rico, Thomas; Denecha, Marine; Caillierez, Raphaelle; Comptdaer, Thomas; Adriaenssens, Eric; Buee, Luc; Lefebvre, Bruno

Document type :

Compte-rendu et recension critique d'ouvrage

DOI :

10.3390/cancers15010116

PMID :

36612113

Permalink :

http://hdl.handle.net/20.500.12210/107962

Title :

Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents

Author(s) :

Rico, Thomas [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
Denecha, Marine [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
Caillierez, Raphaelle [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
Comptdaer, Thomas [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
Adriaenssens, Eric [Auteur]

Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Buee, Luc [Auteur]

Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
Lefebvre, Bruno [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]

Journal title :

Cancers

Pages :

116

Publisher :

MDPI

Publication date :

2023-01

ISSN :

2072-6694

English keyword(s) :

microtubules
double strand DNA breaks
resistance
breast cancer cells
cNHEJ
53BP1

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Popular science :

Non

ANR Project :

Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime

Collections :