Contrasting Role of COMMD5 in Renal Cell Carcinoma: Tumor Suppression and Metastatic Enhancement

Background/Aim: Despite diagnostic and therapeutic advances, renal cell carcinoma (RCC) metastasis remains difficult to eliminate. Copper metabolism MURR1 domain‑containing 5 (COMMD5), a protein involved in tubular epithelial integrity, is implicated in RCC tumorigenesis. This study explored its role in RCC metastasis. Materials and Methods: Proliferation, adhesion, and survival under hypoxia in RCC cells over‑expressing COMMD5 were evaluated. A murine model was used to evaluate metastatic potential in vivo. Clinical data were analyzed for correlations between COMMD5 expression and patient outcomes. Results: COMMD5 over‑expression facilitated cancer cell differentiation and suppressed proliferation but enhanced adhesion and survival under hypoxia. In vivo, it reduced metastatic lung nodule growth but increased the number of metastatic lung nodules. Clinically, high COMMD5 expression in normal kidneys correlated with smaller RCC size, while high COMMD5 expression in tumors was linked to poor metastasis‑free survival. Conclusion: COMMD5 plays dual roles in RCC progression, as a tumor suppressor and a metastasis enhancer.