Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorWilson, TR-
dc.contributor.authorMcEwan, M-
dc.contributor.authorMcLaughlin, K-
dc.contributor.authorLe Clorennec C-
dc.contributor.authorAllen, WL-
dc.contributor.authorFennell, DA-
dc.contributor.authorJohnston, PG-
dc.contributor.authorLongley, DB-
dc.identifier.citationONCOGENE, 2009, 28 (1), pp. 63-72-
dc.description.abstractDeath receptors can directly (type I cells) or indirectly induce apoptosis by activating mitochondrial-regulated apoptosis (type II cells). The level of caspase 8 activation is thought to determine whether a cell is type I or II, with type II cells less efficient at activating this caspase following death receptor activation. FLICE-inhibitory protein (FLIP) blocks death receptor-mediated apoptosis by inhibiting caspase 8 activation; therefore, we assessed whether silencing FLIP could convert type II cells into type I. FLIP silencing-induced caspase 8 activation in Bax wild-type and null HCT116 colorectal cancer cells; however, complete caspase 3 processing and apoptosis were only observed in Bax wild-type cells. Bax-null cells were also more resistant to chemotherapy and tumor necrosis factor-related apoptosis inducing ligand and, unlike the Bax wild-type cells, were not sensitized to these agents by FLIP silencing. Further analyses indicated that release of second mitochondrial activator of caspases from mitochondria and subsequent inhibition of X-linked inhibitor of apoptosis protein (XIAP) was required to induce full caspase 3 processing and apoptosis following FLIP silencing. These results indicate that silencing FLIP does not necessarily bypass the requirement for mitochondrial involvement in type II cells. Furthermore, targeting FLIP and XIAP may represent a therapeutic strategy for the treatment of colorectal tumors with defects in mitochondrial-regulated apoptosis.-
dc.subjectAntineoplastic Agents-
dc.subjectCASP8 and FADD-Like Apoptosis Regulating Protein-
dc.subjectCaspase 3-
dc.subjectCell Line-
dc.subjectColorectal Neoplasms-
dc.subjectGene Silencing-
dc.subjectNeoplasm Staging-
dc.subjectSmall Interfering-
dc.subjectTNF-Related Apoptosis-Inducing Ligand-
dc.subjectX-Linked Inhibitor of Apoptosis Protein-
dc.subjectbcl-2-Associated X Protein-
dc.titleCombined inhibition of FLIP and XIAP induces Bax-independent apoptosis in type II colorectal cancer cells.-
dc.typeJournal Article-
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

Files in This Item:
There are no files associated with this item.

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.