{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CTNNAL1, also known as α‐catulin, is an adaptor/scaffold protein related to the α‐catenin family that plays multifaceted roles in regulating cytoskeletal dynamics, cell adhesion, and signal transduction. In cancer cells, CTNNAL1 has been shown to interact with Rho‐specific guanine nucleotide exchange factors (such as Lbc) to promote RhoA activation and downstream serum response factor signaling, thereby facilitating cytoskeletal reorganization and cell motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In several tumor types—including cervical cancer, melanoma, non‐small cell lung cancer, and head and neck squamous cell carcinoma—upregulated CTNNAL1 contributes to oncogenic processes by modulating β‐catenin and Ras‐dependent signals, enhancing epithelial‐to‐mesenchymal transition (EMT), and promoting invasion, migration, and resistance to apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "7"}]}, {"type": "t", "text": " In melanoma and related cancers, CTNNAL1 not only supports tumor cell proliferation and invasive behavior but also appears to confer chemoresistance through the activation of NF-κB and MAP kinase pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in tumorigenesis, CTNNAL1 is important for maintaining epithelial integrity in the respiratory tract. In human bronchial epithelial cells, CTNNAL1 facilitates wound repair and proliferation—likely by mediating fibronectin-triggered signals that lead to focal adhesion kinase phosphorylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, in models of airway stress and asthma, reduced CTNNAL1 expression is associated with an enhanced EMT phenotype characterized by increased expression of Twist1 and TGF-β1, while its expression inhibits EMT features and excessive mucus secretion through the regulation of YAP and ROCK2 pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that CTNNAL1/α‐catulin acts as a critical regulator of both cancer progression and airway epithelial homeostasis by integrating signals from Rho‐, β‐catenin–, and Ras-dependent pathways to control cytoskeletal organization, cell adhesion, EMT, and related processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brian Park, Nhan T Nguyen, Parmesh Dutt, et al. 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