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 identifie...
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Nature Publishing Group
2023-04-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-00961-x |
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| author | Sunho An Tam Thuy Lu Vo Taekwon Son Hoon Choi Jinyoung Kim Juyeon Lee Byung Hoon Kim Misun Choe Eunyoung Ha Young-Joon Surh Kyu-Won Kim Ji Hae Seo |
| author_facet | Sunho An Tam Thuy Lu Vo Taekwon Son Hoon Choi Jinyoung Kim Juyeon Lee Byung Hoon Kim Misun Choe Eunyoung Ha Young-Joon Surh Kyu-Won Kim Ji Hae Seo |
| author_sort | Sunho An |
| collection | DOAJ |
| description | 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, 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. |
| format | Article |
| id | doaj-art-d4ce04dbbcdb4b258bd7cb70076861a5 |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-d4ce04dbbcdb4b258bd7cb70076861a52025-08-20T03:04:15ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-04-0155477979310.1038/s12276-023-00961-xSAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusionSunho An0Tam Thuy Lu Vo1Taekwon Son2Hoon Choi3Jinyoung Kim4Juyeon Lee5Byung Hoon Kim6Misun Choe7Eunyoung Ha8Young-Joon Surh9Kyu-Won Kim10Ji Hae Seo11College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Biochemistry, School of Medicine, Keimyung UniversityKorea Brain Bank, Korea Brain Research InstituteCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Internal Medicine, School of Medicine, Keimyung UniversityDepartment of Biochemistry, School of Medicine, Keimyung UniversityDepartment of Urology, School of Medicine, Keimyung UniversityDepartment of Pathology, School of Medicine, Keimyung UniversityDepartment of Biochemistry, School of Medicine, Keimyung UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Biochemistry, School of Medicine, Keimyung UniversityAbstract 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.https://doi.org/10.1038/s12276-023-00961-x |
| spellingShingle | Sunho An Tam Thuy Lu Vo Taekwon Son Hoon Choi Jinyoung Kim Juyeon Lee Byung Hoon Kim Misun Choe Eunyoung Ha Young-Joon Surh Kyu-Won Kim Ji Hae Seo SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion Experimental and Molecular Medicine |
| title | SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion |
| title_full | SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion |
| title_fullStr | SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion |
| title_full_unstemmed | SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion |
| title_short | SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion |
| title_sort | samhd1 induced endosomal fak signaling promotes human renal clear cell carcinoma metastasis by activating rac1 mediated lamellipodia protrusion |
| url | https://doi.org/10.1038/s12276-023-00961-x |
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