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Biological Pathway
Cite
Metformin
Metformin inhibits mitochondrial Complex I → reduces intracellular ATP/ADP ratio
reduced oxidative phosphorylation decreases IL-6 autocrine signalling amplitude in tumour microenvironment
JAK1/JAK2 activation by IL-6/IL-6Rα/gp130 complex reduced
STAT3(Tyr705) phosphorylation reduced
STAT3(Tyr705)-unphosphorylated fails to dimerize via reciprocal SH2-pTyr705 interactions
nuclear STAT3 transcriptional activity for BCL-2, MCL-1, cyclin D1, MYC promoters reduced
BCL-2 and MCL-1 mRNA levels reduced → pro-survival signalling diminished
AMPK directly phosphorylates STAT3(Ser727) competing with activating kinases
further STAT3 transactivation domain inhibited
MYC protein reduced
MYC-driven ribosome biogenesis and nucleotide synthesis suppressed
cancer cell proliferation arrested at G1/S via cyclin D1 reduction
Cancer
Score: 0.80
13 hops
Pathway Hops
INHIBITS
Confidence: 95%
INHIBITS
Confidence: 95%
INHIBITS
Confidence: 95%
INHIBITS
Confidence: 95%
PREVENTS
Confidence: 95%
PREVENTS
Confidence: 95%
CAUSES
Confidence: 95%
PHOSPHORYLATES
Confidence: 95%
INHIBITS
Confidence: 95%
SUPPRESSES
Confidence: 95%
SUPPRESSES
Confidence: 95%
CAUSES
Confidence: 95%
PREVENTS
Confidence: 95%
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Metformin → Cancer — Biological Pathway | InTree.AI | InTree