{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRhoJ is a small GTPase belonging to the Rho family that is highly enriched in endothelial cells, where it plays a pivotal role in vascular development and remodeling. Endothelial‐specific transcription factors such as ERG help drive RhoJ expression to regulate key processes including cell migration, tube formation, lumenogenesis, and focal adhesion turnover, as well as endosomal trafficking of proteins like podocalyxin and integrins that are crucial for proper vessel function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its essential role in vascular biology, RhoJ has emerged as an important regulator in cancer progression where its functions can be context dependent. In melanoma, for instance, RhoJ activation—via its downstream effector PAK1—modulates actin dynamics, contributes to chemoresistance by interfering with DNA damage responses, and promotes metastatic dissemination. In glioblastoma and breast cancer, RhoJ enhances cell proliferation, migration, and processes reminiscent of epithelial–mesenchymal transition (EMT) by engaging Rac1/PAK signaling and inflammatory pathways. Conversely, studies in non‐small cell lung cancer (NSCLC) have linked lower RhoJ expression to an accelerated TGF‑β–mediated EMT and poorer clinical outcomes, while in gastric cancer, RhoJ upregulation drives EMT and invasion via IL‑6/STAT3 signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, RhoJ orchestrates its diverse cellular effects by modulating the actin cytoskeleton and governing the trafficking of membrane proteins. Its interaction with complexes like GIT‑PIX facilitates rapid focal adhesion disassembly, while its regulation of endocytic pathways ensures proper recycling of receptors and integrins, thereby influencing extracellular matrix remodeling and lumen formation. Furthermore, RhoJ functions as an integrator of extracellular cues—switching between active and inactive states in response to signals from VEGF and semaphorin 3E—and its unique N‑terminal regulatory domains further fine‐tune nucleotide exchange and membrane association."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "16"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sukhbir Kaur, Katarzyna Leszczynska, Sabu Abraham, et al. 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