{"doi":"10.3389/fonc.2025.1616519","title":"Targeting RAB7 in human B lymphoma by a small molecule inhibitor arrests tumor cell growth","abstract":"RAB7, encoded by RAB7A in humans and Rab7 in mice, is a small GTPase that catalyzes endosome maturation. It mediates NF-κB 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 RAB7A 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 Foxn1 nu/nu nude mice. The inhibitory effect of CID1067700 on Daudi cell growth in vitro is further enhanced by methyl-β-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 RAB7A expression, suggest that targeting RAB7 is a promising therapeutic approach for mature B cell-derived lymphomas.","journal":"Frontiers in Oncology","year":2025,"id":575534,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":567342,"name":"Rui Wang","orcid":"0000-0002-5305-3283","position":1,"is_corresponding":false},{"id":567343,"name":"Jingwei Wang","orcid":"0000-0002-7408-8362","position":2,"is_corresponding":false},{"id":567344,"name":"Shuai Wu","orcid":"0000-0003-1818-0831","position":3,"is_corresponding":false},{"id":1483794,"name":"Kenneth N. Holder","orcid":null,"position":4,"is_corresponding":false},{"id":344442,"name":"Alia Nazarullah","orcid":"0000-0001-7954-6740","position":5,"is_corresponding":false},{"id":409524,"name":"Ricardo C.T. Aguiar","orcid":"0000-0002-8791-5849","position":6,"is_corresponding":false},{"id":288532,"name":"Zijun Y. Xu‐Monette","orcid":"0000-0002-7615-3949","position":7,"is_corresponding":false},{"id":288535,"name":"Ken H. Young","orcid":"0000-0002-5755-8932","position":8,"is_corresponding":false},{"id":567341,"name":"Hui Yan","orcid":"0000-0002-6990-2526","position":9,"is_corresponding":false},{"id":379113,"name":"Zhenming Xu","orcid":"0000-0002-5822-0570","position":10,"is_corresponding":false},{"id":428316,"name":"María E. Fernández","orcid":"0000-0002-4820-821X","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41059303","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}