{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:06:41Z","timestamp":1792796801775,"version":"4.5.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>RAB7, encoded by <jats:italic>RAB7A<\/jats:italic> in humans and <jats:italic>Rab7<\/jats:italic> in mice, is a small GTPase that catalyzes endosome maturation. It mediates NF-\u03baB activation through the assembly of intracellular membrane signalosomes in stimulated normal B cells and plays a B cell-intrinsic role in the antibody response in mice. Here we show <jats:italic>RAB7A<\/jats:italic> transcripts are expressed in primary diffuse large B-cell lymphomas (DLBCLs), and that RAB7 protein expression is heightened in activated human tonsil B cells as well as in DLBCL and Burkitt lymphoma cell lines. Treating these cell lines with CID1067700, a selective small-molecule RAB7 inhibitor, results in a dose-dependent decrease in cell growth, associated with impaired proliferation and survival. CID1067700 also suppressed tumor development from Daudi cells, a Burkitt lymphoma cell line, in <jats:italic>Foxn1<jats:sup>nu\/nu<\/jats:sup><\/jats:italic> nude mice. The inhibitory effect of CID1067700 on Daudi cell growth <jats:italic>in vitro<\/jats:italic> is further enhanced by methyl-\u03b2-cyclodextrin, which disrupts plasma membrane lipid rafts, and by FX1, a BCL6 inhibitor. These findings, together with the unfavorable prognosis of DLBCL patients showing high <jats:italic>RAB7A<\/jats:italic> expression, suggest that targeting RAB7 is a promising therapeutic approach for mature B cell-derived lymphomas.<\/jats:p>","DOI":"10.3389\/fonc.2025.1616519","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T04:12:39Z","timestamp":1758514359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting RAB7 in human B lymphoma by a small molecule inhibitor arrests tumor cell growth"],"prefix":"10.3389","volume":"15","author":[{"given":"Maria","family":"Fernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia","family":"Nazarullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo C. T.","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun Y.","family":"Xu-Monette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken H.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: results from the international\u00a0SCHOLAR-1 study","volume":"130","author":"Crump","year":"2017","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006245","article-title":"Outcomes of patients with large B-cell lymphoma progressing after axicabtagene ciloleucel therapy","volume":"137","author":"Spiegel","year":"2021","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2030164","article-title":"Five-Year outcomes for refractory B-cell lymphomas with CAR T-cell therapy","volume":"384","author":"Chong","year":"2021","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26151","article-title":"2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management","volume":"96","author":"Susanibar-Adaniya","year":"2021","journal-title":"Am J Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101121","article-title":"RelA NF-kappaB subunit activation as a therapeutic target in diffuse large B-cell lymphoma","volume":"8","author":"Zhang","year":"2016","journal-title":"Aging"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3141","article-title":"The germinal center in the pathogenesis of B cell lymphomas","author":"Pasqualucci","year":"2023","journal-title":"Hematol Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1042\/BST20253007","article-title":"ESCRTing the RABs through conversion","volume":"53","author":"Solinger","year":"2025","journal-title":"Biochem Soc Trans"},{"key":"B8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/cells5030034","article-title":"Multiple roles of the small GTPase Rab7","volume":"5","author":"Guerra","year":"2016","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1016\/j.cell.2020.10.039","article-title":"beta-coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway","volume":"183","author":"Ghosh","year":"2020","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401896","article-title":"B cell Rab7 mediates induction of activation-induced cytidine deaminase expression and class-switching in T-dependent and T-independent antibody responses","volume":"194","author":"Pone","year":"2015","journal-title":"J Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601427","article-title":"Small molecule inhibition of Rab7 impairs B cell class switching and plasma cell survival to dampen the autoantibody response in murine lupus","volume":"197","author":"Lam","year":"2016","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901170","article-title":"B cell endosomal RAB7 promotes TRAF6 K63 polyubiquitination and NF-kappaB activation for antibody class-switching","volume":"204","author":"Yan","year":"2020","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1021\/cb3001099","article-title":"A competitive nucleotide binding inhibitor: in vitro characterization of Rab7 GTPase inhibition","volume":"7","author":"Agola","year":"2012","journal-title":"ACS Chem Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2569-8_28","article-title":"Quantitative bead-based flow cytometry for assaying Rab7 GTPase interaction with the Rab-interacting lysosomal protein (RILP) effector protein","volume":"1298","author":"Agola","year":"2015","journal-title":"Methods Mol Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-473702","article-title":"MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program","volume":"122","author":"Xu-Monette","year":"2013","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2296","article-title":"Clinical and biologic significance of MYC genetic mutations in de novo diffuse large B-cell lymphoma","volume":"22","author":"Xu-Monette","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001949","article-title":"A refined cell-of-origin classifier with targeted NGS and artificial intelligence shows robust predictive value in DLBCL","volume":"4","author":"Xu-Monette","year":"2020","journal-title":"Blood Adv"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-495804","article-title":"A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma","volume":"122","author":"Bouamar","year":"2013","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","first-page":"eade8928","DOI":"10.1126\/sciadv.ade8928","article-title":"Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells","volume":"9","author":"Rivera","year":"2023","journal-title":"Sci Adv"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-018-0166-8","article-title":"CID1067700, a late endosome GTPase Rab7 receptor antagonist, attenuates brain atrophy, improves neurologic deficits and inhibits reactive astrogliosis in rat ischemic stroke","volume":"40","author":"Qin","year":"2019","journal-title":"Acta Pharmacol Sin"},{"key":"B21","doi-asserted-by":"publisher","first-page":"102198","DOI":"10.1016\/j.xcrm.2025.102198","article-title":"Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform","volume":"6","author":"Zhang","year":"2025","journal-title":"Cell Rep Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909520199","article-title":"Recruitment of CD40 and tumor necrosis factor receptor-associated factors 2 and 3 to membrane microdomains during CD40 signaling","volume":"275","author":"Hostager","year":"2000","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.13.3304","article-title":"CD40 signaling in human dendritic cells is initiated within membrane rafts","volume":"19","author":"Vidalain","year":"2000","journal-title":"EMBO J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S1074-7613(01)00258-8","article-title":"A CD40 signalosome anchored in lipid rafts leads to constitutive activation of NF-kappaB and autonomous cell growth in B cell lymphomas","volume":"16","author":"Pham","year":"2002","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85795","article-title":"Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma","volume":"126","author":"Cardenas","year":"2016","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1146\/annurev-immunol-020711-075027","article-title":"Pathogenesis of human B cell lymphomas","volume":"30","author":"Shaffer","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1998010","article-title":"Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response","volume":"24","author":"Barish","year":"2010","journal-title":"Genes Dev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1554","article-title":"Tumor-infiltrating normal B cells revealed by immunoglobulin repertoire clonotype analysis are highly prognostic and crucial for antitumor immune responses in DLBCL","volume":"29","author":"Xu-Monette","year":"2023","journal-title":"Clin Cancer Res"}],"updated-by":[{"DOI":"10.3389\/fonc.2025.1711784","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000}}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1616519\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:36:40Z","timestamp":1759743400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1616519\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":28,"alternative-id":["10.3389\/fonc.2025.1616519"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1616519","relation":{"correction":[{"id-type":"doi","id":"10.3389\/fonc.2025.1711784","asserted-by":"object"}]},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]},"article-number":"1616519"}}