{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ladinin‐1 (LAD1) is a collagenous anchoring filament protein primarily located at basement membranes where it plays a central role in maintaining the integrity and cohesion of the dermal–epidermal junction. Several studies have demonstrated that LAD1 is dynamically regulated under different physiological and pathological conditions. For example, its transcription is induced by glucocorticoid receptor signaling in a gene‐selective manner that requires specific Mediator subunits, highlighting its responsiveness to hormonal cues and potential involvement in stress‐related gene regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, an evolutionarily conserved missense polymorphism in LAD1, maintained over millions of years by long‐term balancing selection among primates, underscores its dual role as both a structural protein and an autoantigen in conditions such as linear IgA disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer biology, LAD1 has emerged as an important mediator of cell proliferation, migration, and metastasis. In mammary epithelial cells, epidermal growth factor stimulation leads to LAD1 transcriptional upregulation and phosphorylation, which in turn promotes proliferation and motility via interactions with actin‐binding proteins (e.g., filamins and scaffold proteins like 14-3-3σ)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its aberrant expression has also been linked to aggressive tumor behavior in laryngeal squamous cell carcinoma, where altered anchoring filament expression contributes to changes in cell adhesion and the microenvironment"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "; in prostate cancer, where FGFR1-overexpressing cells show upregulated LAD1 linked to enhanced bone metastases"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "; and in docetaxel-resistant prostate tumors that express high levels of LAD1, correlating with increased invasiveness and poorer outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similar pro-metastatic roles have been observed in colorectal cancer, where LAD1 promotes migration, invasion, and liver metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in cancer, LAD1 has been identified among gene panels associated with metabolic adaptation in high-altitude organisms"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and within proteomic studies that profile cellular interfaces in oral squamous cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, its regulation by estrogen in reproductive tissues suggests possible roles in the modulation of tissue dynamics under hormonal influence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Complementary studies in invertebrate models have indicated that LAD1-related adhesion molecules can also function in developmental processes and morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight that LAD1 is not only essential for maintaining structural integrity and cell–matrix adhesion but also actively participates in cell signaling pathways that regulate proliferation, migration, and invasion. Its dysregulation is linked to tumor aggressiveness and metastatic potential, and its evolutionary conservation and immunogenicity further indicate that LAD1 may serve as both a prognostic biomarker and a potential therapeutic target in diverse diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Weiwei Chen, Inez Rogatsky, Michael J Garabedian "}, {"type": "b", "children": [{"type": "t", "text": "MED14 and MED1 differentially regulate target-specific gene activation by the glucocorticoid receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2005-0318"}], "href": "https://doi.org/10.1210/me.2005-0318"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16239257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16239257"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "João C Teixeira, Cesare de Filippo, Antje Weihmann, et al. 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