Loss of FADD and Caspases Affects the Response of T-Cell
Leukemia Jurkat Cells to Anti-Cancer Drugs

J 2021

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

MRKVOVÁ, Zuzana, Michaela PORTEŠOVÁ and Iva SLANINOVÁ

Basic information

Original name

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

Authors

MRKVOVÁ, Zuzana (203 Czech Republic, belonging to the institution), Michaela PORTEŠOVÁ (203 Czech Republic) and Iva SLANINOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, MDPI, 2021, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.208

RIV identification code

RIV/00216224:14110/21:00121358

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms22052702

UT WoS

000628250300001

Keywords in English

apoptosis; cancer; caspase; cell death; FADD; leukemia; necroptosis; RIP1; RIP3; ripoptosome

Abstract

V originále

Programmed cell death (PCD) pathways play a crucial role in the response of cancer cells to treatment. Their dysregulation is one of the cancer hallmarks and one of the reasons of drug resistance. Here, we studied the significance of the individual members of PCD signaling pathways in response to treatment with common anti-cancer drugs using the T-cell leukemia Jurkat cells with single or double knockouts of necroptosis and/or apoptosis genes. We identified apoptosis as the primary cell death pathway upon anti-cancer drugs treatment. The cells with knocked out either Fas-associated protein with death domain (FADD) or all executioner caspases were resistant. This resistance could be partially overcome by induction of RIP1-dependent necroptosis through TNFR1 activation using combined treatment with TNF-alpha and smac mimetic (LCL161). RIP1 was essential for cellular response to TNF-alpha and smac mimetic, but dispensable for the response to anti-cancer drugs. Here, we demonstrated the significance of FADD and executioner caspases in carrying out programmed cell death upon anti-cancer drug treatments and the ability of combined treatment with TNF-alpha and smac mimetic to partially overcome drug resistance of FADD and/or CASP3/7/6-deficient cells via RIP1-dependent necroptosis. Thus, a combination of TNF-alpha and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis.

Links

MUNI/A/1325/2020, interní kód MU

Name: Biomedicínské vědy

Investor: Masaryk University

Citovat

MRKVOVÁ, Zuzana, Michaela PORTEŠOVÁ and Iva SLANINOVÁ. Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs. International Journal of Molecular Sciences. Basel: MDPI, 2021, vol. 22, No 5, p. 1-16. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms22052702.

@article{1758056,
   author = {Mrkvová, Zuzana and Portešová, Michaela and Slaninová, Iva},
   article_location = {Basel},
   article_number = {5},
   doi = {http://dx.doi.org/10.3390/ijms22052702},
   keywords = {apoptosis; cancer; caspase; cell death; FADD; leukemia; necroptosis; RIP1; RIP3; ripoptosome},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs},
   url = {https://www.mdpi.com/1422-0067/22/5/2702},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1758056
AU  - Mrkvová, Zuzana - Portešová, Michaela - Slaninová, Iva
PY  - 2021
TI  - Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 5
SP  - 1-16
EP  - 1-16
PB  - MDPI
SN  - 14220067
KW  - apoptosis
KW  - cancer
KW  - caspase
KW  - cell death
KW  - FADD
KW  - leukemia
KW  - necroptosis
KW  - RIP1
KW  - RIP3
KW  - ripoptosome
UR  - https://www.mdpi.com/1422-0067/22/5/2702
N2  - Programmed cell death (PCD) pathways play a crucial role in the response of cancer cells to treatment. Their dysregulation is one of the cancer hallmarks and one of the reasons of drug resistance. Here, we studied the significance of the individual members of PCD signaling pathways in response to treatment with common anti-cancer drugs using the T-cell leukemia Jurkat cells with single or double knockouts of necroptosis and/or apoptosis genes. We identified apoptosis as the primary cell death pathway upon anti-cancer drugs treatment. The cells with knocked out either Fas-associated protein with death domain (FADD) or all executioner caspases were resistant. This resistance could be partially overcome by induction of RIP1-dependent necroptosis through TNFR1 activation using combined treatment with TNF-alpha and smac mimetic (LCL161). RIP1 was essential for cellular response to TNF-alpha and smac mimetic, but dispensable for the response to anti-cancer drugs. Here, we demonstrated the significance of FADD and executioner caspases in carrying out programmed cell death upon anti-cancer drug treatments and the ability of combined treatment with TNF-alpha and smac mimetic to partially overcome drug resistance of FADD and/or CASP3/7/6-deficient cells via RIP1-dependent necroptosis. Thus, a combination of TNF-alpha and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis.
ER  -

MRKVOVÁ, Zuzana, Michaela PORTEŠOVÁ and Iva SLANINOVÁ. Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2021, vol.~22, No~5, p.~1-16. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms22052702.

Detailed Information on Publication Record