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Figure 3: Oncogenic activation of PI3K, Akt, and mTOR pathways. Activation of receptor tyrosine kinase activates the PI3K, Akt, and mTOR pathways which leads to the activation of HIF which in turn activates LADH and PDK1 culminating in increased glycolysis and decreased respiration. HIF also activates GLUT 1 and 3, HK I and II ALDA and ALDAC which help in lipid and nucleotide biosynthesis all amplifying the tumor phenotype. p53 reverses this effect by regulating the transcription of three genes, PTEN, TSC2, and AMPK, which then all negatively regulate Akt kinase and mTOR, leading to a decrease in cell growth and a reversal of the cancer phenotype. |