Figure 1.

Schematic overview of the step-wise transformation of renal cysts into cystadenomas and carcinomas, driven by the mTORC1-Fumarate axis. B. Schematic representation of the progressive transformation of cysts into papillae which gradually become cystadenomas and carcinomas. A. The proposed series of events that occurs downstream of the chronic activation of mechanistic target of rapamycin complex 1 (mTORC1). Downregulation of the enzyme fumarate hydratase (FH) leads to the accumulation of the oncometabolite fumarate, previously described to drive a program of epithelial to mesenchymal transition (EMT) though epigenetic regulation. Thus, fumarate-driven EMT along with the metabolic reprogramming and proliferation mediated by the mTORC1 cascade, are likely responsible for the transforming phenotype observed. Part of the images were taken from Servier Medical Art Images (http://smart.servier.com/).