{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEMO1 is an evolutionarily conserved adaptor protein that links receptor tyrosine kinase activation to dynamic cytoskeletal remodeling essential for cell motility. In breast carcinoma cells, activation of ErbB2/HER2 triggers MEMO1‐dependent reorganization of the actin network and coordinated microtubule extension toward the cell cortex, thereby promoting lamellipodia formation and directional migration. Structural studies further reveal that MEMO1 adopts a fold reminiscent of nonheme iron‐dependent dioxygenases and binds specific phosphotyrosine peptides via its vestigial active site, underscoring its role as a molecular relay rather than a conventional enzyme."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its cytoskeletal functions, MEMO1 integrates multiple growth factor and hormone signaling pathways to modulate tumor cell behavior. In various cancers—including breast and colorectal malignancies—heightened MEMO1 expression augments PI3K/Akt and MAPK cascades, fostering epithelial–mesenchymal transition, anchorage-independent growth, and enhanced metastatic potential. MEMO1 interacts with key mediators such as insulin receptor substrates and extranuclear estrogen receptors, thereby fine-tuning receptor signaling and gene expression programs that promote aggressive tumor phenotypes. Moreover, alterations in its regulation (for example, via miRNA targeting) further underscore its importance as an oncogenic driver."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, emerging evidence positions MEMO1 as a critical regulator of redox balance and metal ion homeostasis. It functions as a copper-dependent redox enzyme by coordinating Cu(I) ions to modulate intracellular reactive oxygen species generation, while also binding iron with high affinity in a manner analogous to extradiol dioxygenases—implicating it in ferroptosis and mitochondrial iron delivery. Complementing its roles in cancer, MEMO1 is vital for proper neocortical development by stabilizing microtubule organization in radial glial cells, and its dysregulation—such as through stabilization by proteins like WDR54—can further drive tumor progression in cancers including bladder carcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Romina Marone, Daniel Hess, David Dankort, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Memo is homologous to nonheme iron dioxygenases and binds an ErbB2-derived phosphopeptide in its vestigial active site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703523200"}], "href": "https://doi.org/10.1074/jbc.M703523200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18045866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18045866"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kossay Zaoui, Stéphane Honoré, Daniel Isnardon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Memo-RhoA-mDia1 signaling controls microtubules, the actin network, and adhesion site formation in migrating cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200805107"}], "href": "https://doi.org/10.1083/jcb.200805107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18955552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18955552"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maria Meira, Régis Masson, Igor Stagljar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Memo is a cofilin-interacting protein that influences PLCgamma1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.032094"}], "href": "https://doi.org/10.1242/jcs.032094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19223396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19223396"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A V Sorokin, J Chen "}, {"type": "b", "children": [{"type": "t", "text": "MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.327"}], "href": "https://doi.org/10.1038/onc.2012.327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22824790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22824790"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kai Jiang, Zhihong Yang, Long Cheng, et al. 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