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 ASEP 0500738 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název TRAIL 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 autorů 7 Zdroj.dok. Biochimica Et Biophysica Acta-Molecular Cell Research. - : Elsevier - ISSN 0167-4889
Roč. 1865, č. 3 (2018), s. 522-531Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova TRAIL ; Apoptosis ; Necroptosis ; Receptor-specific signaling Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Vědní obor RIV – spolupráce Ústav molekulární genetiky - Genetika a molekulární biologie CEP ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000430755300006 EID SCOPUS 85039700782 DOI 10.1016/j.bbamcr.2017.12.006 Anotace Tumor 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. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2019
Počet záznamů: 1