Metformin → Cancer — Biological Pathway | InTree.AI

Biological Pathway

MetforminMetformin activates AMPK(Thr172) inhibiting mTORC1(Ser2448 dephosphorylated)mTORC1-dependent MCL-1 cap-dependent translation reduced (MCL-1 has short half-life ~30 min)AMPK phosphorylates GSK3β(Ser9) indirectly via AKT pathway suppressionGSK3β(Tyr216) active form elevatedGSK3β phosphorylates MCL-1(Ser159/Thr163)MCL-1 ubiquitination by FBXW7proteasomal degradationBCL-2(Ser70) phosphorylation status altered: JNK activated by ROS phosphorylates BCL-2(Ser70) converting it from anti- to pro-apoptoticBCL-XL no longer sequesters BAK(Lys113-Asn166 interface)BAK conformational activationBAK(Tyr108)-exposed N-terminus oligomerises in OMMPUMA(BH3 domain) elevated via p53-independent AMPK/FOXO3a axis competes for BCL-2 bindingBAX/BAK pores release cytochrome ccaspase-9(Asp315) activated via apoptosomeCancer

Score: 0.7015 hops

Pathway Hops

ACTIVATESConfidence: 95%

INHIBITSConfidence: 95%

PROMOTESConfidence: 95%

CAUSESConfidence: 95%

INHIBITSConfidence: 95%

RELEASESConfidence: 95%

INDUCESConfidence: 95%

CAUSESConfidence: 95%

PROMOTESConfidence: 95%

ACTIVATESConfidence: 95%

PREVENTSConfidence: 95%

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