In this study, we focused on metabolic regulation in tumor cells during confined migration and demonstrated that IGFBP1, a secreted protein, was upregulated in tumor cells during confined migration, which activated SOD2 to detoxify accumulated ROS in mitochondria by preventing AKT1‐dependent SOD2 phosphorylation, thereby sustaining the survival of confined cells and promoting tumor metastasis (Figure8). Here, AKT1 is linked to neoplasm.