Figure 2

Interaction between different types of programmed cell death and cancer metastasis. Disseminating metastatic cells must face many unfavorable conditions, including detachment from the ECM, attack by immune cells, hypoxia or a growth factor-lacking environment, that cause increased cellular ROS production and DNA damage and insufficient energy status. Low levels of death signals stimulate apoptosis, whereas high levels of death signals often result in necroptosis. Due to the activity of the apoptosis (anoikis) and necroptosis machineries, most metastatic cells from the primary tumor cannot successfully macrometastasize. Compared with apoptosis and necroptosis, autophagy appears to be fairly capricious, as on one hand, autophagy greatly improves the fitness of metastatic cells under stressful conditions to counteract apoptosis and necroptosis, but on the other hand, autophagy reduces metastasis by restricting tumor necrosis and by precluding inflammatory immune cell infiltration. Additionally, excess autophagy induces the death of metastasizing cells.