Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells

Abstract LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration. LDLRAD4 interacts Nedd4 to promote cell proliferation and migration and negatively regulates the TGF-β signaling. Furthermore, immunofluorescence microscopy analysis indicates that LDLRAD4 is localized to the lysosome and association with Nedd4 is necessary for its intracellular transport to the lysosome. In addition, depletion of LDLRAD4 in HepG2 liver cancer cells inhibited tumorigenesis in nude mice. These results reveal an oncogenic role of LDLRAD4 in tumorigenesis through its association with Nedd4.