mTORC1-driven accumulation of the oncometabolite fumarate as a potential critical step in renal cancer progression.

Modeling renal cancer in the mouse has been challenging. We recently showed that upregulation of mechanistic target of rapamycin complex 1 (mTORC1) in a restricted segment of the renal tubule leads to downregulation of the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase, to accumulation of the oncometabolite fumarate, and gradual transformation from benign cysts into cystadenomas and papillary carcinomas.