Both LINP1 and HNF4a knockdown reduced the expression levels of AMPK phosphorylation and WNT5A, indicating for the first time that LINP1 strengthened the HNF4a-AMPK/WNT5A signaling pathway involved in cell glucose metabolism modulation and AML cell survival.
Both ANRIL and AdipoR1 knockdown reduced the expression levels of phosphorylation of AMPK and SIRT1, implying a previously unappreciated ANRIL-AdipoR1-AMPK/SIRT1 signaling pathway in regulating cell glucose metabolism and survival in AML.
AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs.<b>Conclusions:</b> These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1.
AMPK inhibition using the pharmacological inhibitor compound C or by knockdown of PRKAA/AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs.
Our current studies have shown that, the antidiabetic drug metformin also exerts anti-leukemic effect by activating p-AMPK and synergistically sensitizes FLT3 mutated AML to sorafenib.
We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.