Počet záznamů: 1  

TRAIL induces apoptosis but not necroptosis in colorectal and pancreatic cancer cells preferentially via the TRAIL-R2/DR5 receptor

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    SYSNO ASEP0500738
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevTRAIL induces apoptosis but not necroptosis in colorectal and pancreatic cancer cells preferentially via the TRAIL-R2/DR5 receptor
    Tvůrce(i) Nahácka, Zuzana (BTO-N)
    Svadlenka, J. (CZ)
    Peterka, M. (CZ)
    Ksandrova, M. (CZ)
    Benešová, Simona (BTO-N)
    Neužil, Jiří (BTO-N) RID
    Anděra, Ladislav (BTO-N)
    Celkový počet autorů7
    Zdroj.dok.Biochimica Et Biophysica Acta-Molecular Cell Research. - : Elsevier - ISSN 0167-4889
    Roč. 1865, č. 3 (2018), s. 522-531
    Poč.str.12 s.
    Jazyk dok.eng - angličtina
    Země vyd.NL - Nizozemsko
    Klíč. slovaTRAIL ; Apoptosis ; Necroptosis ; Receptor-specific signaling
    Vědní obor RIVEB - Genetika a molekulární biologie
    Obor OECDBiochemistry and molecular biology
    Vědní obor RIV – spolupráceÚstav molekulární genetiky - Genetika a molekulární biologie
    CEPED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
    Institucionální podporaBTO-N - RVO:86652036 ; UMG-J - RVO:68378050
    UT WOS000430755300006
    EID SCOPUS85039700782
    DOI10.1016/j.bbamcr.2017.12.006
    AnotaceTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that can trigger apoptosis in many types of human cancer cells via engagement of its two pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). TRAIL can also activate several other signaling pathways such as activation of stress kinases, canonical NF-κB signaling and necroptosis. Though both receptors are ubiquitously expressed, their relative participation in TRAIL-induced signaling is still largely unknown. To analyze TRAIL receptor-specific signaling, we prepared Strep-tagged, trimerized variants of recombinant human TRAIL with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, we examined the contribution of individual pro-apoptotic receptors to TRAIL-induced signaling pathways. We found that in TRAIL-resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeds comparably via both DR4- and DR5-activated signaling. TRAIL-induced apoptosis, enhanced by the inhibitor of the Bcl-2 family ABT-737, or by the translation inhibitor homoharringtonine, proceeded in both cell lines predominantly via the DR5 receptor. ShRNA-mediated downregulation of DR4 or DR5 receptors in HT-29 cells also pointed to a stronger contribution of DR5 in TRAIL-induced apoptosis. In contrast to apoptosis, necroptotic signaling was activated similarly by both DR4- or DR5-specific ligands. Activation of auxiliary signaling pathways involving NF-κB or stress kinases proceeded under apoptotic conditions mainly in a DR5-dependent manner, while these signaling pathways were during necroptosis similarly activated by either of these ligands. Our study provides the first systematic insight into DR4 −/DR5-specific signaling in colorectal and pancreatic cancer cells.
    PracovištěBiotechnologický ústav
    KontaktMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Rok sběru2019
Počet záznamů: 1  

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