SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.
Autor: | An S; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, South Korea., Vo TTL; Department of Biochemistry, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Son T; Korea Brain Bank, Korea Brain Research Institute, Daegu, 42601, Republic of Korea., Choi H; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, South Korea., Kim J; Department of Internal Medicine, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Lee J; Department of Biochemistry, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Kim BH; Department of Urology, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Choe M; Department of Pathology, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Ha E; Department of Biochemistry, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea., Surh YJ; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, South Korea. surh@snu.ac.kr., Kim KW; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, South Korea. qwonkim@snu.ac.kr., Seo JH; Department of Biochemistry, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea. seojh@kmu.ac.kr. |
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Jazyk: | angličtina |
Zdroj: | Experimental & molecular medicine [Exp Mol Med] 2023 Apr; Vol. 55 (4), pp. 779-793. Date of Electronic Publication: 2023 Apr 03. |
DOI: | 10.1038/s12276-023-00961-x |
Abstrakt: | 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, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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