{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dishevelled‐associated activator of morphogenesis 2 (DAAM2) is a formin family protein that plays multifaceted roles by linking non‐canonical Wnt/planar cell polarity (PCP) signals to the regulation of actin cytoskeletal dynamics. DAAM2 facilitates the transduction of Wnt/PCP signals—activating downstream RHOA cascades and thereby influencing cell polarity, migration, and morphogenesis during development (1,2). In the nervous system, for example, DAAM2 has been implicated in oligodendrocyte function where its activity modulates myelination, and in gut morphogenesis it integrates transcriptional control by factors such as Pitx2 to coordinate actin dynamics and cadherin‐based junction remodeling (3,4). In cardiovascular development, DAAM2 acts redundantly with DAAM1 to support cardiomyocyte polarity and proper heart formation, with combined deficiencies leading to severe noncompaction cardiomyopathy (6)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In disease contexts, alterations in DAAM2 function have emerged as critical events. In cancer, DAAM2 is up‐regulated in several malignancies. Its overexpression in colorectal cancer enhances invasive behavior via activation of PAK1 and increased matrix metalloproteinase‐7 expression (7,10), while in glioma DAAM2 promotes tumorigenesis by binding to and facilitating ubiquitination‐mediated degradation of the tumor suppressor VHL, thus elevating HIF‐1α levels (9). Furthermore, DAAM2 regulation by microRNAs (e.g. miR‑335) underscores its role in tumor cell migration and invasion (7)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have highlighted a role for DAAM2 in non‐neoplastic conditions. Genetic polymorphisms in DAAM2 have been investigated as predictors of renal cell carcinoma risk (5), and variants in DAAM2 have been identified as causative of steroid‐resistant nephrotic syndrome by impairing actin remodeling in podocytes (8). In the placenta, elevated circulating DAAM2 mRNA and increased protein levels in trophoblasts under hypoxic conditions have been associated with fetal growth restriction, suggesting a potential role in placental dysfunction (11). Finally, novel DAAM2 variants have been linked to diffuse pulmonary ossification and have also been observed in aggressive papillary thyroid microcarcinomas (12,13)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings position DAAM2 as a pivotal regulator of actin assembly and cell polarity downstream of Wnt signaling, with essential roles in normal embryonic development and emerging implications in the pathogenesis of diverse human diseases."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "b", "children": [{"type": "t", "text": "Citations:"}]}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masaru Katoh "}, {"type": "b", "children": [{"type": "t", "text": "WNT/PCP signaling pathway and human cancer (review)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16273260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16273260"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhao-Yang Zeng, Yan-Hong Zhou, Wen-Ling Zhang, et al. 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