{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human Lethal giant larvae 1 (LLGL1, also known as Hugl‑1) is the mammalian homolog of the Drosophila tumor suppressor gene lgl and is a critical regulator of epithelial cell polarity, adhesion, and proliferation. LLGL1 is a core component of the Scribble polarity complex, where it cooperates with proteins such as Discs large (Dlg) to maintain apical–basal polarity and proper tissue architecture. Loss or downregulation of LLGL1 has been shown to promote epithelial–mesenchymal transition (EMT) via deregulation of key factors (e.g., reduced E‑cadherin and increased matrix metalloproteinase levels), thereby enhancing cell migration, invasion, and metastasis in a variety of cancers including colorectal, melanoma, endometrial, hepatocellular, and non–small cell lung cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, LLGL1 loss can occur through aberrant splicing or via microRNA targeting—for instance, miR‑652‑3p directly binds the 3′ untranslated region of LLGL1, reducing its expression and further impairing its tumor suppressor function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Beyond its role in epithelial tissues, LLGL1 has been implicated in the regulation of asymmetric cell division and neural stem cell function through interactions with proteins such as ANKLE2 and VRK1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have detailed that LLGL1 interacts with Dlg in a phosphorylation‑dependent manner, which is essential for proper formation of the Scribble complex and maintenance of cell polarity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, LLGL1 protein stability is subject to post‑translational regulation; for example, its deubiquitination by USP11 is dependent on the scaffolding protein RanBPM, and such regulation prevents its proteasomal degradation and sustains its tumor suppressor activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore LLGL1’s central role as a regulator of epithelial polarity and a potent tumor suppressor, with loss or deregulation of LLGL1 contributing to enhanced malignant progression and metastatic potential.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carl C Schimanski, Gösta Schmitz, Anuba Kashyap, et al. 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