Overexpression of IDH2 decreases ROS levels and increases cancer cell growth.121 IDH2 depletion decreases the expression of HIF1α and leads to the attenuation of tumor growth in lung cancer.134 However, because of heterogeneity among cancer cells, other studies have shown that IDH2 expression is decreased in metastatic HCC and gastric cancer tissues compared with paired normal tissues.135,136 The underlying mechanism is that these cells lacking IDH2 show enhanced invasive behavior due to the increase in matrix metalloproteases, which depend on the NF-κB pathway. Here, IDH2 is linked to hepatocellular carcinoma.