Signal transducer and activator of transcription 3 - Forkhead box protein M1 signaling pathway (STAT3-FOXM1 pathway)

The STAT3-FOXM1 signaling pathway is a critical oncogenic axis involved in the progression, metastasis, and therapy resistance of various cancers, including glioblastoma, breast, and lung cancer [1, 2, 7]. STAT3 (Signal Transducer and Activator of Transcription 3) and FOXM1 (Forkhead Box M1) are both transcription factors that often engage in a positive feed-forward loop, where FOXM1 promotes STAT3 expression and activation, and STAT3 in turn regulates FOXM1 transcription [1, 3, 12]. This axis drives the expression of genes essential for cell proliferation, survival, angiogenesis, and the maintenance of cancer stem cell properties [1, 5, 6, 10]. In many malignancies, persistent activation of this pathway is associated with poor prognosis and resistance to conventional chemotherapy and radiotherapy [7, 13]. Therapeutic strategies targeting this axis include direct inhibitors of STAT3 dimerization, JAK inhibitors that block upstream activation, and small molecules or natural products that suppress FOXM1 activity [5, 8, 10]. However, targeting these transcription factors remains challenging due to their lack of traditional small-molecule binding pockets and their essential roles in normal physiological processes like immune regulation and tissue repair [5, 10, 11].

Other names

STAT3/FOXM1 axisSTAT3-FOXM1 signaling axisFoxM1-PDGFA-STAT3 feed-forward pathway

Inhibition of STAT3 phosphorylation and dimerization, suppression of FOXM1 transcriptional activity, and disruption of the STAT3-FOXM1 positive feedback loop.