Fig. 9

Illustrates a pro-tumor mechanism involving the activation of HIF-1α by PDLIM2 downregulation. In lung cancer, decreased PDLIM2 expression leads to NF-κB signaling activation, resulting in impaired SDH gene expression and mitochondrial dysfunction. This dysfunction includes reduced mitochondrial OCR, increased succinate accumulation, elevated mitochondrial fission, and ROS production. Succinate and ROS further inhibit PHD expression, leading to increased HIF-1α activation and ultimately promoting tumor growth. The inhibition of tumor growth by a HIF-1α inhibitor in this study suggests that HIF-1α may be a potential target for treating of cancers resulting from PDLIM2 downregulation