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.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30204 Oncology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW 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
Tags CF PROT, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 5/4/2022 13:41.
Abstract
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 projectName: Funkce HDAC1 v T-buněčných lymfomech
Investor: Czech Science Foundation
LM2018127, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LM2018140, research and development projectName: e-Infrastruktura CZ (Acronym: e-INFRA CZ)
Investor: Ministry of Education, Youth and Sports of the CR
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