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. 2020 Nov 30;11(11):1023. doi: 10.1038/s41419-020-03220-3

Fig. 8. Schematic overview of the functional implication of FL3 on canonical STAT3 and on STAT3/PHB1/SH2D4A signaling in tumor cells.

Fig. 8

Canonical STAT3 signaling is initiated at the plasma membrane by IL-6 binding to its receptor constituted of IL-6 receptor (IL6-R) and gp130. Upon IL-6 binding, JAK1/2 and STAT3 are recruited and activated through phosphorylation. This leads to dimerization of STAT3, translocation to the nucleus and target gene expression. FL3 treatment reduces STAT3 phosphorylation at tyrosine 705 (pSTAT3Y705) and STAT3 transcriptional activity. STAT3 phosphorylated at Serine 727 (pSTAT3S727), PHB and SH2D4A interact in tumor mitochondria and intervention by FL3 leads to imbalances in mitochondrial morphology and reduced mitochondrial respiration.