{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EYA2 is a multifunctional protein that plays pivotal roles both during normal development and in disease. In embryogenesis, EYA2 acts as a transcriptional coactivator and protein tyrosine phosphatase that cooperates with SIX family transcription factors to regulate early myogenic commitment and the specification of various progenitor cell populations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, its phosphatase activity contributes to the cellular response to DNA damage through dephosphorylation of the histone H2A.X tyrosine residue, thereby modulating repair signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, aberrant EYA2 expression underpins aggressive tumor behavior. In breast cancer, EYA2 functions as an essential co‐factor for SIX1, bolstering transforming growth factor‐β signaling, epithelial–mesenchymal transition (EMT), and cancer stem cell properties, which altogether promote metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, genetic variations affecting EYA2 are linked to overall survival in non‐small cell lung cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while its elevated expression in ovarian tumors correlates with poor clinical outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the regulatory level, EYA2 expression is modulated by microRNAs. For instance, miR-338-3p and miR-30a have been shown to directly target EYA2, leading to its downregulation and consequent inhibition of oncogenic phenotypes in breast and lung cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, EYA2 is implicated in neurological disorders; it is identified as a direct target of MeCP2 in a mouse model of Rett syndrome, suggesting a contribution to the disease’s complex phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies underscore that EYA2 is a critical regulator of both developmental processes and oncogenic mechanisms. Its dual roles—as a mediator of gene activation in partnership with SIX proteins during organogenesis and as a driver of tumor progression through modulation of transcriptional programs and DNA repair—highlight its potential as a promising diagnostic marker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Raphaelle Grifone, Josiane Demignon, Julien Giordani, et al. 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