Nischarin interaction with LGR4 mediates the suppression of the Wnt/β-catenin signaling pathway.

Nischarin is a potent breast tumor suppressor that regulates cell migration and influences various signaling pathways by interacting with Rac1, Pak1, Rab14, STK11/LKB1, LIMK, and AMPK. Through co-immunoprecipitation (Co-IP) experiments, we confirmed that Nischarin associates with the leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4). When full-length Nischarin was transfected into MDA-MB 231 and HEK 293 T cells, which naturally express low levels of Nischarin, key components of the WNT signaling pathway, including Axin1, β-catenin, cyclin D1, Dvl 2, and LRP6 proteins, were significantly suppressed, and the LGR4-RANKL-GSK-3β signaling pathway was also inhibited. Consistent with previous studies, when Nischarin was knocked down in commonly used neural cell lines such as PC 12 and Neuro 2a, several proteins in the WNT signaling pathway were upregulated, and neurite elongation was enhanced. Our findings elucidate an important role of Nischarin in LGR4-WNT signaling pathway.