Details

Autor(en) / Beteiligte

• An, Sunho
• Vo, Tam Thuy Lu
• Son, Taekwon
• Choi, Hoon
• Kim, Jinyoung
• Lee, Juyeon
• Kim, Byung Hoon
• Choe, Misun
• Ha, Eunyoung
• Surh, Young-Joon
• Kim, Kyu-Won
• Seo, Ji Hae

Titel

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

Ist Teil von

• Experimental and Molecular Medicine, 2023, 55(0), , pp.779-793

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Kidney cancer: Protein involved in cancer spread explored A protein that is overexpressed in kidney cancer drives metastasis by regulating a specific pathway, and provides a potential therapeutic target. Sunho An at Seoul National University, South Korea, and co-workers examined the role of the SAMHD1 protein in the promotion and metastasis of renal clear cell carcinoma. SAMHD1 mutations are found in multiple cancers and have been linked to resistance to chemotherapy. The team analysed extensive datasets and found that high levels of SAMHD1 expression are associated with poor prognoses. Using human cell cultures, they showed that the protein is involved in processes that facilitate the migration and invasion of cancer cells. For example, SAMHD1 binds to another protein and promotes the formation of lamellipodia, protrusions on the leading edge of the cancer cell membrane that aid migration, by inducing a particular signaling pathway.