Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.13336
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dc.titleAberrant localization of apoptosis protease activating factor-1 in lipid raft sub-domains of diffuse large B cell lymphomas
dc.contributor.authorHirpara, J.L
dc.contributor.authorLoh, T
dc.contributor.authorNg, S.B
dc.contributor.authorChng, W.J
dc.contributor.authorPervaiz, S
dc.date.accessioned2020-10-31T11:44:21Z
dc.date.available2020-10-31T11:44:21Z
dc.date.issued2016
dc.identifier.citationHirpara, J.L, Loh, T, Ng, S.B, Chng, W.J, Pervaiz, S (2016). Aberrant localization of apoptosis protease activating factor-1 in lipid raft sub-domains of diffuse large B cell lymphomas. Oncotarget 7 (51) : 83964-83975. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.13336
dc.identifier.issn1949-2553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/182520
dc.description.abstractResistance to chemotherapy remains a challenge in the clinical management of diffuse B cell lymphomas despite aggressive chemotherapy such as CHOP and monoclonal CD20. Here we provide evidence that the apoptosome adaptor protein, Apaf-1, is mislocalized in primary cells derived from patients with diffuse large B cell lymphomas (DLBCL). Whereas, the total expression of Apaf-1 did not change, its subcellular localization was significantly different in DLBCL, compared to T cell lymphomas as well as cells derived from reactive lymphadenopathy biopsies. As expected, Apaf-1 was detected in the cytosolic fractions of non-B cell lymphomas and non-cancerous tissues; however, in B cell derived lymphomas the protein was detected in membrane raft sub-domains rather than the cytosol. Disruption of lipid raft structures resulted in the redistribution of Apaf-1 to the cytosol and restored apoptosis sensitivity of DLBCL. Furthermore, we identified novel small molecule compounds that target DLBCL by promoting Apaf-1 release form lipid rafts via mechanisms that involve an increase in intracellular reactive oxygen species production. Taken together, our results implicate Apaf-1 mislocalization as a potential diagnostic and prognostic marker for DLBCL, and provide a novel therapeutic strategy for circumventing the drug refractory nature of this sub-class of B cell lymphoma.
dc.publisherImpact Journals LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectapoptotic protease activating factor 1
dc.subjectreactive oxygen metabolite
dc.subjectantineoplastic agent
dc.subjectAPAF1 protein, human
dc.subjectapoptotic protease activating factor 1
dc.subjectCASP3 protein, human
dc.subjectcaspase 3
dc.subjectreactive oxygen metabolite
dc.subjectapoptosis
dc.subjectArticle
dc.subjectbiopsy
dc.subjectcell level
dc.subjectcontrolled study
dc.subjectcytosol
dc.subjectdiffuse large B cell lymphoma
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectlipid raft
dc.subjectlymphadenopathy
dc.subjectprimary cell
dc.subjectprotein expression
dc.subjectprotein localization
dc.subjectprotein secretion
dc.subjectT cell lymphoma
dc.subjectapoptosis
dc.subjectdiffuse large B cell lymphoma
dc.subjectdrug effects
dc.subjectdrug resistance
dc.subjectgenetics
dc.subjectJurkat cell line
dc.subjectlipid peroxidation
dc.subjectmembrane microdomain
dc.subjectmetabolism
dc.subjectpathology
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.subjectAntineoplastic Agents
dc.subjectApoptosis
dc.subjectApoptotic Protease-Activating Factor 1
dc.subjectCaspase 3
dc.subjectCell Line, Tumor
dc.subjectDrug Resistance, Neoplasm
dc.subjectHumans
dc.subjectJurkat Cells
dc.subjectLipid Peroxidation
dc.subjectLymphoma, Large B-Cell, Diffuse
dc.subjectMembrane Microdomains
dc.subjectReactive Oxygen Species
dc.subjectSignal Transduction
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF OTOLARYNGOLOGY
dc.contributor.departmentDEPT OF PATHOLOGY
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.18632/oncotarget.13336
dc.description.sourcetitleOncotarget
dc.description.volume7
dc.description.issue51
dc.description.page83964-83975
dc.published.statepublished
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