Signal transducer and activator of transcription 3 (STAT3) and Extracellular signal-regulated kinase (ERK) signaling pathways (STAT3/ERK)

The Signal transducer and activator of transcription 3 (STAT3) and Extracellular signal-regulated kinase (ERK) signaling pathways represent a critical integrated regulatory network that governs essential cellular processes. STAT3 is a latent transcription factor that, upon activation by Janus kinases (JAKs) or growth factor receptors, undergoes phosphorylation and translocates to the nucleus to drive the expression of genes involved in cell survival, proliferation, and immune suppression [1]. The ERK pathway, a core component of the Mitogen-Activated Protein Kinase (MAPK) cascade, is typically triggered by Ras and Raf proteins to regulate cell cycle progression and differentiation [2]. These two pathways frequently converge, with ERK-mediated phosphorylation of STAT3 at the Ser727 residue serving as a key mechanism to modulate and often enhance STAT3's transcriptional activity [3]. In many human cancers and inflammatory diseases, both pathways are constitutively active, promoting tumor progression, epithelial-mesenchymal transition, and resistance to conventional therapies [4]. Consequently, the STAT3/ERK axis is a major focus of drug development, with therapeutic strategies involving the use of small molecule inhibitors or antisense oligonucleotides to disrupt these signaling nodes and restore normal cellular homeostasis [5]. Sources: [1] UniProt (P40763) [2] UniProt (P27361/P28482) [3] Science (1997) 278(5344):1809-1812 [4] Cancers (Basel) (2018) 10(9):312 [5] Int J Mol Sci (2017) 18(5):938

Other names

STAT3-ERK axisSTAT3/MAPK signaling pathwayJAK/STAT and Ras/MAPK crosstalkSTAT3/ERK1/2 signaling

Inhibition of STAT3 SH2 domain dimerization, inhibition of MEK1/2 or ERK1/2 catalytic activity, and disruption of STAT3 phosphorylation and nuclear translocation.