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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Hematologic Malignancies

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1616519

Targeting RAB7 in human B lymphoma by a small molecule inhibitor arrests tumor cell growth

Provisionally accepted
Maria FernandezMaria Fernandez1Rui WangRui Wang1Jingwei WangJingwei Wang1Kenneth HolderKenneth Holder2Alia NazarullahAlia Nazarullah2Ricardo AguiarRicardo Aguiar3Hui YanHui Yan1*Zhenming XuZhenming Xu1
  • 1Department of Microbiology, Immunology and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, United States
  • 2Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, United States
  • 3Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, United States

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RAB7, encoded by RAB7A in humans and Rab7 in mice, is a small GTPase that catalyzes endosome maturation. It mediates NF-kB 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 Foxn1nu/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.

Keywords: B cells, B cell lymphoma, Burkitt Lymphoma, CID1067700, Diffuse large B-cell lymphoma, FX1, MβCD, NF-kB

Received: 23 Apr 2025; Accepted: 05 Sep 2025.

Copyright: © 2025 Fernandez, Wang, Wang, Holder, Nazarullah, Aguiar, Yan and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hui Yan, Department of Microbiology, Immunology and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material