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Model of metformin’s affect on TNBC cells.
In this model, PTGS1, which encode COX1 (cyclooxygenase 1), is transcriptionally repressed by metformin. As COX1 activity is decreased, PERK is activated, and phosphorylates EIF2a. Phosphorylated EIF2α in turn causes selective translation of ATF4, which in turn contributes to DDIT3 gene expression. DDIT3 then regulates expression of antiproliferative genes. Among these is GDF15, which has been associated with senescence in cancer.
