Figure 3.

Mechanisms by which heme oxygenase 1 (HO-1) may contribute to cancer progression. (A) Signal peptidases (SPPs) mediate HO-1 compartmentation to the nucleus, where it regulates the expression of vascular endothelial growth factor (VEGF), promoting angiogenesis and invasion. CO, in a tumorigenic environment, may also promote the same previous effect. HO-1 also regulates nuclear erythroid 2-related factor (Nrf2) expression, which in turn regulates the expression of antioxidant enzymes such as HO-1, G6PH, and NQO1, enhancing the antioxidant capacities of the tumor cells. (B) HO-1 expressing macrophages are polarized into M2 state, promoting anti-inflammatory pathways and facilitating cancer cell to evade the immune system. In colorectal cancer (CRC) cells, the overexpression of HO-1 results in low levels of ICAM-1 and CXCL-10, reducing T-cell adhesion and recruitment.