LGL-3SA

LGL-3SA is a non-phosphorylatable, constitutively active mutant form of the tumor suppressor protein Lethal Giant Larvae (Lgl). In glioblastoma multiforme (GBM), the loss of PTEN leads to the activation of the PI3K pathway, which results in the constitutive phosphorylation and subsequent inactivation of Lgl. LGL-3SA is engineered with serine-to-alanine mutations at its phosphorylation sites, rendering it resistant to this inactivation. Research conducted at the Ottawa Hospital Research Institute has shown that LGL-3SA expression reduces the invasiveness of glioblastoma cells by impairing the trafficking of matrix metalloproteinase 14 (MMP14) to the cell surface, thereby preventing the degradation of the extracellular matrix. This mutant protein has been evaluated in preclinical models, including in vitro cell cultures and in vivo intracranial xenografts, as a potential therapeutic strategy to combat the highly invasive nature of glioblastoma.

Other names

non-phosphorylatable Lglconstitutively active Lgl