{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:01:05Z","timestamp":1791223265047,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,6,11]],"date-time":"2008-06-11T00:00:00Z","timestamp":1213142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30471586"],"award-info":[{"award-number":["30471586"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Basic Research Program of China"},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["2004AA215162"],"award-info":[{"award-number":["2004AA215162"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA123490"],"award-info":[{"award-number":["R01 CA123490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["6249-05"],"award-info":[{"award-number":["6249-05"]}],"id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["6033-08"],"award-info":[{"award-number":["6033-08"]}],"id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interestingly, some lymphoma cells, expressing high levels of transmembrane (tm)TNF-\u03b1, are resistant to secretory (s)TNF-\u03b1-induced necrosis but sensitive to tmTNF-\u03b1-mediated apoptosis. As tmTNF-\u03b1 mediates \u201cforward\u201d as well as \u201creverse\u201d signaling, we hypothesize that a balanced signaling between forward and reverse directions may play a critical role in determining the fate of cells bearing tmTNF-\u03b1. Using Raji cells as a model, we first added exogenous tmTNF-\u03b1 on fixed, transfected NIH3T3 cells onto Raji cells to examine tmTNF-\u03b1 forward signaling and its effects, showing that constitutive NF-\u03baB activity and cellular inhibitor-of-apoptosis protein 1 transcription were down-regulated, paralleled with Raji cell death. As Raji cells express tmTNF-\u03b1, an inhibition of their tmTNF-\u03b1 expression by antisense oligonucleotide caused down-regulation of NF-\u03baB activity. Conversely, increasing tmTNF-\u03b1 expression by suppressing expression of TNF-\u03b1-converting enzyme that cleaves tmTNF-\u03b1 led to an enhanced activation of NF-\u03baB, indicating that tmTNF-\u03b1, but not sTNF-\u03b1, contributes to constitutive NF-\u03baB activation. We next transfected Raji cells with a mutant tmTNF-\u03b1 lacking the intracellular domain to competitively suppress reverse signaling via tmTNF-\u03b1; as expected, constitutive NF-\u03baB activity was decreased. In contrast, treating Raji cells with sTNFR2 to stimulate reverse signaling via tmTNF-\u03b1 ehanced NF-\u03baB activation. We conclude that tmTNF-\u03b1, when highly expressed on tumor cells and acting as a receptor, promotes NF-\u03baB activation through reverse signaling, which is helpful to maintain tumor cell survival. On the contrary, tmTNF-\u03b1, when acting as a ligand, inhibits NF-\u03baB activity through forward signaling, which is inclined to induce tumor cell death.<\/jats:p>","DOI":"10.1189\/jlb.0208078","type":"journal-article","created":{"date-parts":[[2008,6,13]],"date-time":"2008-06-13T01:25:58Z","timestamp":1213320358000},"page":"789-797","source":"Crossref","is-referenced-by-count":65,"title":["Transmembrane TNF-\u03b1 mediates \u201cforward\u201d and \u201creverse\u201d signaling, inducing cell death or survival via the NF-\u03baB pathway in Raji Burkitt lymphoma cells"],"prefix":"10.1093","volume":"84","author":[{"given":"Hailong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalin","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjiao","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology\/BMT, Emory University School of Medicine , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,6,11]]},"reference":[{"key":"2023032712464432100_","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signaling pathways of the TNF superfamily: a double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. 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