Lethal giant larvae protein homolog 1 (LLGL1) (LLGL1)

Lethal giant larvae protein homolog 1 (LLGL1) is a critical evolutionary conserved tumor suppressor and scaffolding protein that plays a fundamental role in establishing and maintaining apico-basal cell polarity (UniProt Q15334; PubMed 22431510). It functions as part of the Scribble polarity complex, alongside Scribble (SCRIB) and Discs large (DLG), where it antagonizes the Par complex to define the basolateral membrane domain (PubMed 25670684). In many human malignancies, LLGL1 is frequently downregulated or mislocalized, leading to a loss of cellular architecture, increased epithelial-to-mesenchymal transition (EMT), and enhanced metastatic potential (PubMed 22431510; NCBI Gene 3996). While no direct pharmacological activators of LLGL1 are currently in clinical use, it is a significant focus of research for its role in cancer progression and as a potential biomarker for prognosis (PubMed 32671048). Therapeutic strategies often focus on inhibiting the kinases that negatively regulate LLGL1, such as atypical protein kinase C (aPKC), to restore its tumor-suppressive functions (PubMed 25670684).

Other names

HUGL-1LGL1LLGLMLLGLLethal giant larvae homolog 1Lgl

Restoration of cell polarity and suppression of epithelial-mesenchymal transition (EMT) through stabilization of the Scribble/Dlg/Lgl complex.