To further understand the functional aspects of ADAMTS1 in VCAN cleavage, invasion, and promotion of anoikis resistance, we observed that inactivating the metalloproteinase activity of ADAMTS1 with an E402Q mutation significantly reduced the enhanced VCAN cleavage, invasive ability, and anoikis resistance in RCC cells. Here, ADAMTS1 is linked to renal cell carcinoma.