Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24
dc.contributor.author | Ekmekcioglu, Suhendan | |
dc.contributor.author | Mumm, John B. | |
dc.contributor.author | Udtha, Malini | |
dc.contributor.author | Chada, Sunil | |
dc.contributor.author | Grimm, Elizabeth A. | |
dc.date | 2022-08-11T08:08:52.000 | |
dc.date.accessioned | 2022-08-23T16:10:32Z | |
dc.date.available | 2022-08-23T16:10:32Z | |
dc.date.issued | 2008-05-31 | |
dc.date.submitted | 2009-02-24 | |
dc.identifier.citation | Cytokine. 2008 Jul;43(1):34-44. Epub 2008 Jun 3. <a href="http://dx.doi.org/10.1016/j.cyto.2008.04.010">Link to article on publisher's site</a> | |
dc.identifier.issn | 1096-0023 (Electronic) | |
dc.identifier.doi | 10.1016/j.cyto.2008.04.010 | |
dc.identifier.pmid | 18511292 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/32957 | |
dc.description.abstract | Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1-regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN-alpha) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN-gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN-beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN-beta induction followed by IRF regulation and TRAIL/FasL system activation. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18511292&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1016/j.cyto.2008.04.010 | |
dc.subject | Cell Death; Cell Line; Cell Line, Tumor; Coculture Techniques; Humans; Interferon-alpha; Interferon-beta; Interleukins; Melanoma; Signal Transduction; Up-Regulation | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24 | |
dc.type | Journal Article | |
dc.source.journaltitle | Cytokine | |
dc.source.volume | 43 | |
dc.source.issue | 1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/1509 | |
dc.identifier.contextkey | 738077 | |
html.description.abstract | <p>Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1-regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN-alpha) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN-gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN-beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN-beta induction followed by IRF regulation and TRAIL/FasL system activation.</p> | |
dc.identifier.submissionpath | gsbs_sp/1509 | |
dc.contributor.department | Department of Molecular Genetics and Microbiology | |
dc.contributor.department | Department of Experimental Therapeutics | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 34-44 |