Rhof, also known as Ras homolog family member F, filopodia associated, is a member of the Rho guanosine triphosphatase (GTPase) family. Rho GTPases cycle between GDP-bound inactive and GTP-bound active states to control many signaling pathways. Rhof has been implicated in various cell functions such as long filopodia formation, adhesion, and migration [3]. It is involved in multiple biological processes and diseases, with its role studied in different cell types and disease models.

In pancreatic cancer, Rhof overexpression accelerates cell proliferation, migration, and invasion, while inhibiting apoptosis. It promotes endothelial-mesenchymal transition (EMT) and glycolysis, acting through the c-Myc/PKM2 axis to induce Snail1 lactylation [1]. In acute myeloid leukemia (AML), Rhof is overexpressed, correlating with a poor prognosis. Gain-and loss-of-function experiments in vitro and in a human AML xenograft mouse model showed that Rhof enhances AML cell proliferation and impedes apoptosis, and its down-regulation combined with chemotherapy has significant therapeutic efficacy in vivo. Mechanistically, it activates the AKT/β-catenin signaling pathway [2]. In murine models, RhoF knockout led to a significant reduction in marginal zone (MZ) B cells in the spleen, suggesting it promotes MZ B cell development [4].

In conclusion, Rhof plays crucial roles in multiple biological processes and disease conditions. Studies using gene knockout mouse models have revealed its oncogenic role in pancreatic cancer and AML, as well as its function in B-cell development. Understanding Rhof's functions provides potential therapeutic targets for diseases like pancreatic cancer, AML, and insights into B-cell-related immunological processes [1,2,4].

References:

1. Zhao, Rui, Yi, Yanmin, Liu, Han, Wang, Lei, Li, Feng. 2024. RHOF promotes Snail1 lactylation by enhancing PKM2-mediated glycolysis to induce pancreatic cancer cell endothelial-mesenchymal transition. In Cancer & metabolism, 12, 32. doi:10.1186/s40170-024-00362-2. https://pubmed.ncbi.nlm.nih.gov/39462429/

2. Wen, Xin, Li, Peng, Ma, Yuechan, Ye, Jingjing, Ji, Chunyan. 2024. RHOF activation of AKT/β-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance. In iScience, 27, 110221. doi:10.1016/j.isci.2024.110221. https://pubmed.ncbi.nlm.nih.gov/39021805/

3. Sugawara, Ryota, Ueda, Hiroshi, Honda, Ryo. 2019. Structural and functional characterization of fast-cycling RhoF GTPase. In Biochemical and biophysical research communications, 513, 522-527. doi:10.1016/j.bbrc.2019.04.018. https://pubmed.ncbi.nlm.nih.gov/30981505/

4. Kishimoto, Mayuko, Matsuda, Takenori, Yanase, Shougo, Matsushita, Tadashi, Maruyama, Mitsuo. . Rhof promotes murine marginal zone B cell development. In Nagoya journal of medical science, 76, 293-305. doi:. https://pubmed.ncbi.nlm.nih.gov/25741038/