Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance

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Authors

ABAD Etna CIVIT Laia POTĚŠIL David ZDRÁHAL Zbyněk LYAKHOVICH Alex

Year of publication 2021
Type Article in Periodical
Magazine / Source FEBS Journal
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://doi.org/10.1111/febs.15588
Doi http://dx.doi.org/10.1111/febs.15588
Keywords cancer stem cells; chemoresistance; DNA damage repair; RAD50; triple- negative breast cancer
Description A growing body of evidence supports the notion that cancer resistance is driven by a small subset of cancer stem cells (CSC), responsible for tumor initiation, growth, and metastasis. Both CSC and chemoresistant cancer cells may share common qualities to activate a series of self-defense mechanisms against chemotherapeutic drugs. Here, we aimed to identify proteins in chemoresistant triple-negative breast cancer (TNBC) cells and corresponding CSC-like spheroid cells that may contribute to their resistance. We have identified several candidate proteins representing the subfamilies of DNA damage response (DDR) system, the ATP-binding cassette, and the 26S proteasome degradation machinery. We have also demonstrated that both cell types exhibit enhanced DDR when compared to corresponding parental counterparts, and identified RAD50 as one of the major contributors in the resistance phenotype. Finally, we have provided evidence that depleting or blocking RAD50 within the Mre11-Rad50-NBS1 (MRN) complex resensitizes CSC and chemoresistant TNBC cells to chemotherapeutic drugs.
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