PTEN and nonpapillary renal cell carcinoma: In contrast, pairing Cyclin D with ccRCC-associated mutations upstream in the PI3K or MAPK pathway, such as PI3K/mTORC1/ERK hyper-activation or p21/PTEN loss [114], only led to weak cell cycle rescue (S7C Fig, top); though most of these combinations also mildly boosted EMT (S7C Fig, bottom).