{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe metastasis‐suppressor proteins NME1 and NME2 (also known as Nm23-H1 and Nm23-H2) have been shown to play a pivotal role in regulating cell adhesion and metastasis. For example, in squamous carcinoma cells, overexpression of plakoglobin induces a mesenchymal-to-epidermoid transition that is accompanied by an increase in Nm23-H1 mRNA and Nm23-H2 protein levels. Detailed biochemical and imaging analyses revealed that Nm23-H2, in particular, interacts with plakoglobin, cadherins, and alpha-catenin—mainly within the cytoskeleton-associated protein pool. This interaction, which requires the N-terminal domain of plakoglobin, is thought to stabilize Nm23 expression and contribute to its metastasis suppressor activity, offering a potential mechanism for the tumor/metastasis-suppressing function of plakoglobin itself."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther studies in related systems have characterized molecular regulators that, while distinct from NME1/2, underscore the broad theme of intricate control over cellular differentiation and signal transduction. One investigation into hematopoietic lineage commitment identified a novel gene—MYADM—with promoter characteristics conferring preferential activity in myeloid cells, hinting at specialized roles in cell identity and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, research in the context of pulmonary immunity has uncovered that MYADM—a membrane-associated differentiation marker—functions as a binding partner for surfactant protein A, mediating eosinophil apoptosis and impacting airway inflammation in asthma, thus highlighting the importance of transmembrane signaling proteins in modulating immune cell fate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Meanwhile, another study on m6A RNA modifications has linked the m6A reader Ythdf2 with the proliferation of pulmonary artery smooth muscle cells, reinforcing the view that a spectrum of regulatory pathways governs cellular behavior in both oncogenic and nononcogenic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Z Aktary, K Chapman, L Lam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.495"}], "href": "https://doi.org/10.1038/onc.2009.495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20101217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20101217"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Karin Dannaeus, Marina Bessonova, Jan-Ingvar Jönsson "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the mouse myeloid-associated differentiation marker (MYADM) gene: promoter analysis and protein localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-005-0753-x"}], "href": "https://doi.org/10.1007/s11033-005-0753-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16172915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16172915"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alane Blythe C Dy, Paul R Langlais, Natalie K Barker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-02869-w"}], "href": "https://doi.org/10.1038/s41598-021-02869-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34862427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34862427"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jie Wang, Yueyao Shen, Yuhui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.124.22801"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.124.22801"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38832511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38832511"}]}]}]}