Scribble–Dlg–Lgl1 polarity complex (Scribble complex)

The Scribble–Dlg–Lgl1 polarity complex is a fundamental protein module responsible for the establishment and maintenance of apicobasal cell polarity in epithelial and endothelial tissues (Bilder and Perrimon, 2000; NIH). It consists of three core components: Scribble (SCRIB), Discs large (DLG1), and Lethal giant larvae (LLGL1), which cooperatively localize to the basolateral membrane domain (Elsum et al., 2012; ResearchGate). This complex acts as a potent tumor suppressor by scaffolding signaling pathways that control cell proliferation, such as the Hippo, Notch, and Ras/MAPK pathways, and by maintaining tissue architecture through the regulation of adherens and tight junctions (Stephens et al., 2018; PubMed). In many human cancers, the Scribble complex is frequently downregulated or mislocalized from the cell membrane to the cytoplasm, a transition that correlates with epithelial-to-mesenchymal transition (EMT), increased invasiveness, and poor clinical prognosis (Humbert et al., 2003; NIH). Therapeutic interventions are being explored to restore the complex's function, including the use of APT2 inhibitors to stabilize Scribble's membrane-anchoring palmitoylation or targeting downstream oncogenic effectors like YAP/TAZ (Cell Chemical Biology, 2017; biorxiv).

Other names

Scribble moduleScribble polarity moduleScribble-Dlg-Lgl complexSCRIB-DLG1-LLGL1 complexBasolateral polarity complex

Restoration of membrane localization via inhibition of depalmitoylation (e.g., APT2 inhibitors) or inhibition of downstream oncogenic signaling pathways (e.g., Hippo/YAP, Notch, and MAPK) activated upon complex disruption.