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.