PMC

Chemotherapeutic drugs have various modes of action but ultimately integrate signals with the FOXO3a-FOXM1 signaling axis. FOXO3a then antagonizes the expression of FOXM1 target genes, which control cancer-related processes, including cell cycle progression, cell proliferation, anti-oxidative stress, cell self-renewal, drug resistance, DNA damage repair, senescence suppression, angiogenesis, and migration. RTK, receptor tyrosine kinase; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositol-3-kinase.

Intracellular and extracellular signals converge on the PI3K-AKT-FOXO3a-FOXM1 signaling cascade. FOXO3a antagonizes the transcription output of FOXM1, which controls cancer-related processes including proliferation, survival, drug resistance, angiogenesis, migration, and DNA damage repair. EGFR, human epidermal growth factor receptor; HER-2, human epidermal growth factor receptor 2; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; P38, P38 mitogen-activated protein kinase; P53, tumor suppressor protein 53; E2F, E2F transcription factor; ER, estrogen receptor; E2, estradiol; ATM, ataxia telangiectasia mutated protein; Ub, ubiquitination; P, phosphorylation.