{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Macrophage‐capping protein (CAPG) is a member of the gelsolin/villin family that regulates actin dynamics by binding and “capping” the barbed ends of actin filaments in a calcium‐dependent manner. CAPG has emerged as a multifunctional regulator influencing cell motility, invasion, and metastasis in a variety of pathophysiological settings. In several tumor models—including breast, ovarian, colon, gastric, renal, and brain cancers—CAPG up‐regulation correlates with enhanced cell migration, invasive behavior, and poorer clinical outcomes; indeed, high CAPG levels in primary tumors have been associated with increased risk of bone metastasis and reduced overall survival, and its knockdown can attenuate migratory and invasive capacities of tumor cells"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": ", and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, CAPG transcription is induced under hypoxic conditions through direct binding of hypoxia‐inducible factor‐1α (HIF‑1α) to its promoter"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and noncoding RNAs (e.g., circular RNA circ_CAPG) can stabilize CAPG mRNA to promote chemoresistance in glioma by modulating Wnt/β‑catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In other settings, CAPG influences key processes beyond cancer. For example, it participates in fibroblast activation during extracellular matrix remodeling in the post‐ischemic heart"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", modulates endothelial cell motility in response to shear stress associated with atherosclerotic plaque‐free flow"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and is up‐regulated in activated monocytes and macrophages in inflammatory contexts"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "and upon exposure to wear particles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Furthermore, CAPG expression has been evaluated as a potential diagnostic and prognostic biomarker in malignancies such as cholangiocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", renal cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and glioma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", and its absolute quantification in tissues has been accomplished using advanced immunoblot techniques."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Interestingly, naturally occurring genetic variants of CAPG—as well as alterations in its expression following viral infection"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "or upon treatment with traditional herbal medicine"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "—further underscore its regulatory versatility. Finally, foundational studies have detailed CAPG’s structure, calcium‐binding properties, and evolutionary relationship with other actin regulators"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", while analyses in experimental glioblastoma and canine lymphoma have reinforced its relevance as a biomarker"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " Collectively, these findings indicate that CAPG plays a central role in modulating the cytoskeleton to control cell motility, which in turn impacts tumor progression, metastasis, inflammation, tissue remodeling, and immune regulation "}, {"type": "b", "children": [{"type": "t", "text": "(1,2,3,4,5,6,8,9,10,13,14,15,19,20,21,22,23,24,26,27,28,29,30,31)"}]}, {"type": "t", "text": ".\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "i", "children": [{"type": "t", "text": "Note:"}]}, {"type": "t", "text": " Additional studies have also implicated CAPG in regulating gene expression during endometrial receptivity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "and in age‐related alterations of immune cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jules A Westbrook, David A Cairns, Jianhe Peng, et al. 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