Lethal giant larvae homolog 2 (LLGL2)

Lethal giant larvae homolog 2 (LLGL2) is a scaffolding protein that plays a critical role in establishing and maintaining apicobasal cell polarity in epithelial tissues (UniProt Q6P1M3). It is a member of the evolutionary conserved Scribble polarity complex, which includes Scribble and Discs large (Dlg), and functions by interacting with atypical protein kinase C (aPKC) and Par6 to regulate the spatial organization of the cytoskeleton (NCBI Gene: 3993). While traditionally viewed as a tumor suppressor due to its role in maintaining tissue architecture, recent studies have identified LLGL2 as a promoter of tumor growth in specific contexts, such as estrogen receptor-positive (ER+) breast cancer (Saito et al., 2019, Nature). In these cases, LLGL2 helps cells survive nutrient stress by facilitating the membrane localization of nutrient transporters like SLC7A5 (LAT1). Consequently, LLGL2 is emerging as a potential therapeutic target for cancers that exploit polarity proteins for metabolic adaptation (PubMed: 31413363). Currently, there are no clinical-stage drugs targeting LLGL2, but research is ongoing to understand its role in drug resistance and metastasis.

Other names

LGL2HUGL2HUGL-2Human giant larvae homolog 2

Inhibition of LLGL2-mediated nutrient transporter stabilization or disruption of the Scribble/Dlg/Lgl complex