1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.133
Figure 4 Activation of the PI3K–mTOR pathway in clear cell renal cell carcinoma (ccRCC)
Figure 4 | Activation of the PI3K–mTOR pathway in clear cell renal cell carcinoma (ccRCC). Genomic abnormalities that affect various components of the PI3K–mTOR signalling pathway can result in activation of this pathway. Activating mutations are observed in genes that encode the components of PI3K, AKT and mTOR, whereas genomic loss or inactivating mutations are recurrently found in negative regulators of the signalling pathway, including PTEN and TSC1. Activation or upregulation of receptor tyrosine kinases (RTKs), which act upstream of the PI3K complex, enhance the abnormal activity of this signalling pathway. Abnormally activated mTOR induces multiple cellular processes that promote malignancy, including increased protein translation, cell proliferation and aggression. Notably mTOR activity also increases levels of HIF-α and thereby fuels the upregulation of HIF-mediated gene expression, which promotes angiogenesis and reprogramming of the metabolic activity of cells toward glycolysis (that is, a Warburg-like effect).
Riazalhosseini, Y. & Lathrop, M. (2016) Precision medicine from the renal cancer genome
Nat. Rev. Nephrol. doi: /nrneph