Skip to main content
. Author manuscript; available in PMC: 2020 May 13.
Published in final edited form as: Cell Rep. 2019 Dec 17;29(12):4086–4098.e6. doi: 10.1016/j.celrep.2019.11.079

Figure 6. Metformin Prevents Pro-tumorigenic Bidirectional Signaling between Tumor and Mesothelial Cells.

Figure 6.

Modulation of tumor-stromal crosstalk by metformin inhibits OvCa tumor progression. Left: OvCa-derived CM or TGF-β1 inhibits PHD activation in mesothelial cells, resulting in HIF1α stabilization and the subsequent induction of IL-8 and CCL2, promoting tumor progression. Right: metformin inhibits TGF-β1 from OvCa cells to impede tumor-mesothelial cell crosstalk, thereby maintaining PHD activity and the concomitant degradation of HIF1α in mesothelial cells. This effect of metformin is mechanistically linked to a reduction in SUCLG2 and succinate and ultimately prevents the stroma-derived signaling required for OvCa colonization and invasion of the omentum.