Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy

Figure 2

Illustration of mTOR signaling and tumor relationship. Mammalian target of rapamycin (mTORC1) expression is regulated by mTORC2 through Akt/TSC1/2/Rheb signaling pathway that leads to overactivation of mTORC1 and finally results in proliferation and metastasis and encourages tumor formation. In given figure, mutation in cell and extracellular growth signals activate mTORC1 that results in phosphorylation of RNF168 and ubiquitination of H2AFX and H2AX (histone). Overall, the pathway end ups with DNA damage that leads to tumor formation (tumorigenesis). Similarly, mTORC2 activates Akt signaling that promotes binding of Rheb to TSC1/2. It leads to ubiquitination of Rheb, and its activity is reduced. Finally, reduction in Rheb downregulation takes place that triggers mTORC1 activation and inhibits tumor growth. MMP-9 and B7-H1 is upregulated through the mTOR signaling pathway after activation of mTORC1 and results in cancer metastasis and invasion. Abbreviations: mTORC1: mammalian target of rapamycin complex 1; mTORC2: mammalian target of rapamycin complex 2; Akt: serine/threonine-protein kinase; TSC1/2: tuberous sclerosis 1and 2; Rheb: Ras homolog enriched in brain; H2AFX, MMP-9: matrix metalloproteinase–9.