Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.13336
DC Field | Value | |
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dc.title | Aberrant localization of apoptosis protease activating factor-1 in lipid raft sub-domains of diffuse large B cell lymphomas | |
dc.contributor.author | Hirpara, J.L | |
dc.contributor.author | Loh, T | |
dc.contributor.author | Ng, S.B | |
dc.contributor.author | Chng, W.J | |
dc.contributor.author | Pervaiz, S | |
dc.date.accessioned | 2020-10-31T11:44:21Z | |
dc.date.available | 2020-10-31T11:44:21Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Hirpara, 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.issn | 1949-2553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/182520 | |
dc.description.abstract | Resistance 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.publisher | Impact Journals LLC | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | apoptotic protease activating factor 1 | |
dc.subject | reactive oxygen metabolite | |
dc.subject | antineoplastic agent | |
dc.subject | APAF1 protein, human | |
dc.subject | apoptotic protease activating factor 1 | |
dc.subject | CASP3 protein, human | |
dc.subject | caspase 3 | |
dc.subject | reactive oxygen metabolite | |
dc.subject | apoptosis | |
dc.subject | Article | |
dc.subject | biopsy | |
dc.subject | cell level | |
dc.subject | controlled study | |
dc.subject | cytosol | |
dc.subject | diffuse large B cell lymphoma | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | human tissue | |
dc.subject | lipid raft | |
dc.subject | lymphadenopathy | |
dc.subject | primary cell | |
dc.subject | protein expression | |
dc.subject | protein localization | |
dc.subject | protein secretion | |
dc.subject | T cell lymphoma | |
dc.subject | apoptosis | |
dc.subject | diffuse large B cell lymphoma | |
dc.subject | drug effects | |
dc.subject | drug resistance | |
dc.subject | genetics | |
dc.subject | Jurkat cell line | |
dc.subject | lipid peroxidation | |
dc.subject | membrane microdomain | |
dc.subject | metabolism | |
dc.subject | pathology | |
dc.subject | signal transduction | |
dc.subject | tumor cell line | |
dc.subject | Antineoplastic Agents | |
dc.subject | Apoptosis | |
dc.subject | Apoptotic Protease-Activating Factor 1 | |
dc.subject | Caspase 3 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Humans | |
dc.subject | Jurkat Cells | |
dc.subject | Lipid Peroxidation | |
dc.subject | Lymphoma, Large B-Cell, Diffuse | |
dc.subject | Membrane Microdomains | |
dc.subject | Reactive Oxygen Species | |
dc.subject | Signal Transduction | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DEPT OF OTOLARYNGOLOGY | |
dc.contributor.department | DEPT OF PATHOLOGY | |
dc.contributor.department | DEPT OF MEDICINE | |
dc.contributor.department | DEPT OF PHYSIOLOGY | |
dc.description.doi | 10.18632/oncotarget.13336 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 7 | |
dc.description.issue | 51 | |
dc.description.page | 83964-83975 | |
dc.published.state | published | |
Appears in Collections: | Elements Staff Publications |
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