{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCN5 (also known as WISP2) is emerging as a multifunctional matricellular protein that plays important context‐dependent roles in modulating cell differentiation, invasion, and tissue remodeling. In estrogen receptor–positive breast cancer cells, CCN5 acts as a transcriptional repressor by associating with histone deacetylase 1 to downregulate key mediators of the transforming growth factor‐β (TGF‑β) cascade, such as the TGF‑β type II receptor; this, in turn, restricts TGF‑β–induced epithelial–mesenchymal transition (EMT) and limits invasive behavior, thereby contributing to maintenance of a differentiated, low‐invasive phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the cardiovascular context, transgenic expression studies have demonstrated that CCN5 counteracts the pro‐hypertrophic and pro‐fibrotic actions of other CCN family members—such as CCN2—thereby mitigating cardiac hypertrophy and fibrosis and preserving myocardial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In mesenchymal precursor cells, the secreted form of CCN5 can activate the canonical WNT signaling pathway, leading to stabilization and nuclear accumulation of β‑catenin, which in turn impedes peroxisome proliferator–activated receptor γ (PPARγ) induction and the subsequent adipogenic differentiation; this dual intracellular and extracellular regulation thereby helps maintain an undifferentiated state or directs alternative lineage commitment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these studies illustrate that CCN5 functions as a negative regulator of EMT and invasion in breast cancer cells, an anti‐remodeling agent in cardiac tissue, and a modulator of mesenchymal cell differentiation, highlighting its potential as both a prognostic marker and a therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michèle Sabbah, Céline Prunier, Nathalie Ferrand, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-1461"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-1461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18794149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18794149"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pyoung Oh Yoon, Min-Ah Lee, Hyeseon Cha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2010.04.010"}], "href": "https://doi.org/10.1016/j.yjmcc.2010.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20430035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20430035"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "John R Grünberg, Ann Hammarstedt, Shahram Hedjazifar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Novel Secreted Adipokine WNT1-inducible Signaling Pathway Protein 2 (WISP2) Is a Mesenchymal Cell Activator of Canonical WNT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.511964"}], "href": "https://doi.org/10.1074/jbc.M113.511964"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24451367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24451367"}]}]}]}