LGI3 increases human keratinocyte migration

Abstract

We recently found that that leucine‐rich glioma inactivated 3 (LGI3) is expressed in human skin. However, the physiological roles of LGI3 in human keratinocytes remain unknown. In the present study, it was demonstrated that LGI3 acts as a stimulator for human HaCaT keratinocyte migration without affecting cell viability and proliferation. Western blot analysis showed that LGI3 induced FAK activation, Akt phosphorylation, and GSK‐3β phosphorylation in HaCaT cells. Further study demonstrated that LY294002, a selective PI3K inhibitor and LiCl, a selective GSK‐ 3β inhibitor abrogated the increased cell migration induced by LGI3. Next, we examined β‐catenin levels after LGI3 treatment, because the Akt‐GSK‐3β pathway is known to regulate accumulation of β‐catenin, which is an important mediator of cell migration. LGI3 treatment increased β‐catenin protein level and nuclear localization, whereas LY294002 prevented LGI3‐induced FAK and Akt activation as well as β‐catenin accumulation. Taken together, it is suggested that LGI3 stimulates HaCaT cell migration via the accumulation of β‐catenin through the Akt pathway. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011‐0026587).