SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.

ABSTRACT: Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, w

SUBMITTER: An S 

PROVIDER: S-EPMC10167369 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature