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

J 2021

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

ABAD, Etna, Laia CIVIT, David POTĚŠIL, Zbyněk ZDRÁHAL, Alex LYAKHOVICH et. al.

Basic information

Original name

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

Authors

ABAD, Etna, Laia CIVIT, David POTĚŠIL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution) and Alex LYAKHOVICH (643 Russian Federation, guarantor, belonging to the institution)

Edition

FEBS Journal, Hoboken, Wiley, 2021, 1742-464X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.622

RIV identification code

RIV/00216224:14740/21:00118829

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1111/febs.15588

UT WoS

000584017500001

Keywords in English

cancer stem cells; chemoresistance; DNA damage repair; RAD50; triple- negative breast cancer

Abstract

V originále

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.

Links

GF19-29701L, research and development project

Name: Funkce HDAC1 v T-buněčných lymfomech

Investor: Czech Science Foundation, Partner Agency (Austria)

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

ABAD, Etna, Laia CIVIT, David POTĚŠIL, Zbyněk ZDRÁHAL and Alex LYAKHOVICH. Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance. FEBS Journal. Hoboken: Wiley, 2021, vol. 288, No 7, p. 2184-2202. ISSN 1742-464X. Available from: https://dx.doi.org/10.1111/febs.15588.

@article{1730032,
   author = {Abad, Etna and Civit, Laia and Potěšil, David and Zdráhal, Zbyněk and Lyakhovich, Alex},
   article_location = {Hoboken},
   article_number = {7},
   doi = {http://dx.doi.org/10.1111/febs.15588},
   keywords = {cancer stem cells; chemoresistance; DNA damage repair; RAD50; triple- negative breast cancer},
   language = {eng},
   issn = {1742-464X},
   journal = {FEBS Journal},
   title = {Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance},
   url = {https://doi.org/10.1111/febs.15588},
   volume = {288},
   year = {2021}
}

TY  - JOUR
ID  - 1730032
AU  - Abad, Etna - Civit, Laia - Potěšil, David - Zdráhal, Zbyněk - Lyakhovich, Alex
PY  - 2021
TI  - Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance
JF  - FEBS Journal
VL  - 288
IS  - 7
SP  - 2184-2202
EP  - 2184-2202
PB  - Wiley
SN  - 1742464X
KW  - cancer stem cells
KW  - chemoresistance
KW  - DNA damage repair
KW  - RAD50
KW  - triple- negative breast cancer
UR  - https://doi.org/10.1111/febs.15588
L2  - https://doi.org/10.1111/febs.15588
N2  - 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.
ER  -

ABAD, Etna, Laia CIVIT, David POTĚŠIL, Zbyněk ZDRÁHAL and Alex LYAKHOVICH. Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance. \textit{FEBS Journal}. Hoboken: Wiley, 2021, vol.~288, No~7, p.~2184-2202. ISSN~1742-464X. Available from: https://dx.doi.org/10.1111/febs.15588.

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