Signal transducer and activator of transcription 3 and Mitogen-activated protein kinase signaling components (STAT3/MAPK)

Signal transducer and activator of transcription 3 (STAT3) and Mitogen-activated protein kinase (MAPK) signaling components are critical nodes in intracellular pathways that regulate cell proliferation, survival, and immune responses [1.2.1, 1.3.1]. STAT3 is a latent transcription factor activated by Janus kinases (JAKs) or growth factor receptors, which then translocates to the nucleus to drive the expression of genes involved in oncogenesis and inflammation [1.2.3, 1.3.4]. The MAPK pathway, including ERK, JNK, and p38, responds to extracellular stimuli to modulate similar cellular processes [1.3.1, 1.3.4]. Dysregulation of these pathways is a hallmark of various cancers, including lung, gastric, and melanoma, as well as chronic inflammatory conditions like psoriasis and fibrosis [1.2.1, 1.2.4, 1.3.4]. Therapeutic strategies target these components using small molecule inhibitors and monoclonal antibodies, but efficacy is often challenged by complex crosstalk and compensatory mechanisms between the two pathways [1.3.2, 1.4.1].

Other names

STAT3 pathwayMAPK pathwayJAK/STAT and Ras/Raf/MEK/ERK pathwaysSTAT3/MAPK axisSignal transducer and activator of transcription 3 and Mitogen-activated protein kinase signaling

Inhibition of STAT3 phosphorylation, dimerization (SH2 domain), or DNA binding; inhibition of MAPK cascade kinases (e.g., MEK, BRAF, ERK) catalytic activity [1.2.3, 1.3.1, 1.4.2].