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. 2017 Sep 11;9(11):10135–10146. doi: 10.18632/oncotarget.20807

Figure 2. The representative mechanisms underlying tumour suppression by metformin and berberine.

Figure 2

(1) LKB1/AMPK/mTORC1 axis. PI3K/Akt inhibits TSC1/TSC2, leading to increases in Rheb-GTP and mTOR activation. Metformin increases levels of AMP and thus promotes activation of AMPK through LKB1 phosphorylation of T172, which by phosphorylation in turn inhibits raptor and activates the TSC1/TSC2 complex, an GTPase activating protein for Rheb, culminating in inhibition of mTORC1. (2) Both metformin and berberine can attenuate EMT. In addition, berberine activates AMPK to execute cellular functions by a mechanism similarly to metformin.