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

Date Published: 2025-09-22

Abstract:
RAB7, encoded by RAB7A in humans and Rab7 in mice, is a small GTPase that catalyzes endosome maturation. It mediates NF-?B 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-?-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.

Introduction:
Many B cell malignancies have less than 60% 10-year survival rate under current therapies ( 1 – 4 ). New therapeutic targets are urgently needed, particularly those that are involved in NF-?B activation, a key factor in B cell lymphoma pathogenesis and therapy resistance ( 5 , 6 ). RAB7 is a small GTPase encoded by RAB7A in humans and Rab7 in mice. In addition to serving as the marker of mature endosomes and early lysosomes, RAB7 mediates the generation of mature endosomes from immature endosomes that are marked…

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