4.1.2 Rapamycin effects on cancer
To fuel proliferative growth and division, tumor cells must reprogram their energy metabolism to maintain an adequate energy supply—a process that is regulated by the mTORC 1 complex. First, the activation of mTORC1 promotes aerobic glycolysis by increasing the amount of hypoxia inducible factor (HIF)-1α, a transcription factor that is associated with metastasis by promoting angiogenesis responding to hypoxia 139. Also, activated mTORC1 increases lipid synthesis by phosphorylating Lipin-1 and S6K1, thereby activating sterol regulatory element binding factor (SREBP)-1, a lipogenic transcription factor whose binding to the genes involved in lipogenesis upregulates their transcription 140, 141.
Moreover, mTORC1-mediated phosphorylation of S6K1 can enhance the biosynthesis of purine and pyrimidine, two amino acids that are required for cancer cell proliferation 142 . Indeed, over-activation of mTORC1 signaling has been observed in many types of cancer such as lymphoma, endometrial cancer, and renal cell carcinoma143-145. Therefore, as a potent inhibitor of mTOR 1, rapamycin can put a brake on the defective tumor metabolism and thus is considered as a promising drug for combating cancer.