malfunction |
the expression of transforming growth factor beta (TGFbeta) is significantly reduced in APE1-deficient osteosarcoma cells. Transforming growth factor beta promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. APE1, TGFbeta, and microvessel density (MVD) have a pairwise correlation in osteosarcoma tissue samples, whereas TGFbeta, tumor size, and MVD are inversely related to the prognosis of the cohort. High expression of APE1, TGFbeta, and microvessel density (MVD) correlate with poor prognosis of osteosarcoma patients. Apurinic/apyrimidinic endonuclease 1-siRNA-mediated downregulation in osteosarcoma cells inhibits expression of TGFbeta1. Apurinic/apyrimidinic endonuclease 1-siRNA inhibits the capability to enhance HUVEC migration and tube formation of tumor cells through the TGFbeta/Smad3 signaling pathway. Tumor angiogenesis and growth in xenografts are suppressed by APE1-siRNA |
Homo sapiens |
physiological function |
apurinic/apyrimidinic endonuclease 1 is a multifunctional protein playing crucial roles in DNA base excision repair and redox regulation of gene expression, activities that are functionally and structurally independent of each other. The APE1 redox activity stimulates numerous transcriptional factors, including activator protein-1 (AP-1), nuclear factor-kappaB (NF-happaB), and HIF-1. These factors are involved in mediating VEGF gene expression; HIF-1 and NF-kappaB, in particular, increased VEGF expression in response to hypoxia. Apurinic/apyrimidinic endonuclease 1 (APE1) is a dually functional protein possessing both base excision repair and redox activities, it is involved in tumor angiogenesis. APE1, TGFbeta, and microvessel density (MVD) have a pairwise correlation in osteosarcoma tissue samples, whereas TGFbeta, tumor size, and MVD are inversely related to the prognosis of the cohort. High expression of APE1, TGFbeta, and microvessel density (MVD) correlate with poor prognosis of osteosarcoma patients. APE1 may indirectly regulate angiogenesis through a TGFbeta-dependent pathway |
Homo sapiens |