Radiotherapy is one of the major therapeutic strategies for human non-small cell lung cancer (NSCLC), but intrinsic radioresistance of cancer cells makes a further improvement of radiotherapy for NSCLC challenging. Mitochondrial function is frequently dysregulated in cancer cells for adaptation to the changes of tumour microenvironment after exposure to radiation.
A study led by Fuxiang Zhou at the Zhongman Hospital of Wuham University in China found that down-regulation of single-strand DNA-binding protein 1 (SSBP1) in H1299 cells was associated with inducing mitochondrial dysfunction and increasing radiosensitivity to ionizing radiation. Furthermore, SSBP1 loss induced mitochondrial dysfunction via decreasing mitochondrial DNA copy number and ATP generation, enhancing the mitochondrial-derived reactive oxygen species accumulation and down regulating key glycolytic enzymes expression. Researchers also observed that SSBP1 knockdown increased the radiosensitivity of H1299 cells by inducing increased apoptosis, prolonged G2/M phase arrest and defective homologous recombination repair of DNA double-strand breaks.
The results from this study suggest that SSBP1 is a radioresistance-related protein, providing potential novel mitochondrial target for sensitizing NSCLC to radiotherapy.
Other studies have shown that SSBP1 is associated with changes in metabolic status in human cancer cells. The level of SSBP1 protein correlates with the aggressiveness of human osteosarcoma cells, suggesting a link between mitochondrial DNA replication and cancer progression. SSBP1 has also been found to suppress epithelial-to-mesenchymal transition and metastasis in triple-negative breast cancer.