Our observation that XMU-MP-1 could inhibit VHL−/− ccRCC growth not only in soft agar (3D cultures) but also in 2D cultures, a condition in which HIF-2α is dispensable, implied that YAP may inhibit VHL−/− ccRCC growth through additional mechanism(s). Here, EPAS1 is linked to nonpapillary renal cell carcinoma.