[WS8-2] がん細胞と間質細胞での酸素センシング機構の制御はがん進展を制御する
Tumor is a dynamic tissue remodeled by the interaction between cancer and stromal cells, and has a unique microenvironment with diverse levels of oxygen from severe hypoxia/anoxia to normoxia. Hypoxia inducible factor (HIF) plays an essential role to adapt to such diverse oxygen levels for cells in tumor tissues; HIF controls cellular functions such as invasion, angiogenesis, metabolism, and stemness in cancer and stromal cells and thereby promotes tumor malignancy. Under hypoxic conditions that are characteristic of tumors, HIF becomes active due to the decreased activities of oxygen-dependent HIF suppressors; HIF prolyl hydroxylase domain containing proteins (PHDs) and factor-inhibiting HIF-1 (FIH-1). In addition, recent studies have revealed that HIF activity under normoxic conditions also promotes tumor progression by promoting glycolysis in cancer cells and macrophages. Hitherto, we have identified Mint3 as a HIF activator under normoxia by suppressing FIH-1 and revealed the regulatory mechanisms of HIF activation by Mint3 in cancer cells and macrophages. Here, we show how Mint3 controls tumor progression in cancer and stromal cells and discuss the possibility of anti-tumor microenvironment drugs targeting Mint3.