Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620548
Title:
Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells.
Authors:
Sosna, Justyna; Philipp, Stephan; Fuchslocher Chico, Johaiber; Saggau, Carina; Fritsch, Jürgen; Föll, Alexandra; Plenge, Johannes; Arenz, Christoph; Pinkert, Thomas; Kalthoff, Holger; Trauzold, Anna; Schmitz, Ingo; Schütze, Stefan; Adam, Dieter
Abstract:
Recently, a type of regulated necrosis (RN) called necroptosis was identified to be involved in many pathophysiological processes and emerged as an alternative method to eliminate cancer cells. However, only a few studies have elucidated components of TRAIL-mediated necroptosis useful for anticancer therapy. Therefore, we have compared this type of cell death to tumor necrosis factor (TNF)-mediated necroptosis and found similar signaling through acid and neutral sphingomyelinases, the mitochondrial serine protease HtrA2/Omi, Atg5, and vacuolar H(+)-ATPase. Notably, executive mechanisms of both TRAIL- and TNF-mediated necroptosis are independent of poly(ADP-ribose) polymerase 1 (PARP-1), and depletion of p38α increases the levels of both types of cell death. Moreover, we found differences in signaling between TNF- and TRAIL-mediated necroptosis, e.g., a lack of involvement of ubiquitin carboxyl hydrolase L1 (UCH-L1) and Atg16L1 in executive mechanisms of TRAIL-mediated necroptosis. Furthermore, we discovered indications of an altered involvement of mitochondrial components, since overexpression of the mitochondrial protein Bcl-2 protected Jurkat cells from TRAIL- and TNF-mediated necroptosis, and overexpression of Bcl-XL diminished only TRAIL-induced necroptosis in Colo357 cells. Furthermore, TRAIL does not require receptor internalization and endosome-lysosome acidification to mediate necroptosis. Taken together, pathways described for TRAIL-mediated necroptosis and differences from those for TNF-mediated necroptosis might be unique targets to increase or modify necroptotic signaling and eliminate tumor cells more specifically in future anticancer approaches.
Affiliation:
Helmholtz Centre for infection research
Citation:
Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells. 2016, 36 (20):2626-44 Mol. Cell. Biol.
Journal:
Molecular and cellular biology
Issue Date:
15-Oct-2016
URI:
http://hdl.handle.net/10033/620548
DOI:
10.1128/MCB.00941-15
PubMed ID:
27528614
Type:
Article
Language:
en
ISSN:
1098-5549
Appears in Collections:
publications of the AG system-oriented immunologyand infection research (SIME)

Full metadata record

DC FieldValue Language
dc.contributor.authorSosna, Justynaen
dc.contributor.authorPhilipp, Stephanen
dc.contributor.authorFuchslocher Chico, Johaiberen
dc.contributor.authorSaggau, Carinaen
dc.contributor.authorFritsch, Jürgenen
dc.contributor.authorFöll, Alexandraen
dc.contributor.authorPlenge, Johannesen
dc.contributor.authorArenz, Christophen
dc.contributor.authorPinkert, Thomasen
dc.contributor.authorKalthoff, Holgeren
dc.contributor.authorTrauzold, Annaen
dc.contributor.authorSchmitz, Ingoen
dc.contributor.authorSchütze, Stefanen
dc.contributor.authorAdam, Dieteren
dc.date.accessioned2016-10-12T13:09:09Z-
dc.date.available2016-10-12T13:09:09Z-
dc.date.issued2016-10-15-
dc.identifier.citationDifferences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells. 2016, 36 (20):2626-44 Mol. Cell. Biol.en
dc.identifier.issn1098-5549-
dc.identifier.pmid27528614-
dc.identifier.doi10.1128/MCB.00941-15-
dc.identifier.urihttp://hdl.handle.net/10033/620548-
dc.description.abstractRecently, a type of regulated necrosis (RN) called necroptosis was identified to be involved in many pathophysiological processes and emerged as an alternative method to eliminate cancer cells. However, only a few studies have elucidated components of TRAIL-mediated necroptosis useful for anticancer therapy. Therefore, we have compared this type of cell death to tumor necrosis factor (TNF)-mediated necroptosis and found similar signaling through acid and neutral sphingomyelinases, the mitochondrial serine protease HtrA2/Omi, Atg5, and vacuolar H(+)-ATPase. Notably, executive mechanisms of both TRAIL- and TNF-mediated necroptosis are independent of poly(ADP-ribose) polymerase 1 (PARP-1), and depletion of p38α increases the levels of both types of cell death. Moreover, we found differences in signaling between TNF- and TRAIL-mediated necroptosis, e.g., a lack of involvement of ubiquitin carboxyl hydrolase L1 (UCH-L1) and Atg16L1 in executive mechanisms of TRAIL-mediated necroptosis. Furthermore, we discovered indications of an altered involvement of mitochondrial components, since overexpression of the mitochondrial protein Bcl-2 protected Jurkat cells from TRAIL- and TNF-mediated necroptosis, and overexpression of Bcl-XL diminished only TRAIL-induced necroptosis in Colo357 cells. Furthermore, TRAIL does not require receptor internalization and endosome-lysosome acidification to mediate necroptosis. Taken together, pathways described for TRAIL-mediated necroptosis and differences from those for TNF-mediated necroptosis might be unique targets to increase or modify necroptotic signaling and eliminate tumor cells more specifically in future anticancer approaches.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleDifferences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection researchen
dc.identifier.journalMolecular and cellular biologyen

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