Research Paper Advance Articles pp 23478—23496

Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells

Figure 10. Proposed mechanism of the regulation of galectin-9 expression in human cancer and embryonic stage at low and normal oxygen availability stages. The figure depicts the key processes taking place in embryonic development and malignant tumour growth during the initial low oxygen availability (hypoxic) stage and later (normal oxygen availability) stages. The studied biochemical events are demonstrated in the right-hand panel. During the hypoxic stage, HIF-1 induces TGF-β expression, which then displays autocrine activity and triggers galectin-9 expression in a Smad3-dependent manner. During the normal oxygen availability stage, AP-1 contributes to TGF-β expression but it is also self-triggered by TGF-β. Galectin-9 upregulation is perpetually induced by the TGF-β-Smad3 pathway.