The Function And Mechanism Of The Novel Regulator TF20 In Glucose Metabolism Of Cancer Cells

Cancer cells rely mainly on glycolysis for energy,with active glycolysis and high metabolite lactate content,which was known as the "Warburg effect".Transcription factors play an important role in the regulation of glucose metabolism in tumor cells.Although transcription factors,such as p53,HIF1α,and SIX1,have been shown to regulate glucose metabolism,the process of glucose metabolism regulation remains largely unknown.With transcriptome sequencing,we found for the first time that the transcription factor TF20 regulated glucose metabolism of cancer cells.Further glycolytic ability experiments and cell proliferation experiments confirmed that TF20 regulates the glycolysis of breast cancer cells,which in turn affects the proliferation of breast cancer cells.Luciferase reporter assay and chromatin immunoprecipitation(Ch IP)experiments showed that TF20 inhibits transcription of metabolic enzymes by binding to the promoters of the glycolytic genes HK2,ALDOA and PGK1.Co-immunoprecipitation experiments showed that TF20 interacts with histone deacetylase SIRT6.Further experiments indicated that TF20 regulates the transcription and expression of HK2,ALDOA,and PGK1 in a SIRT6-dependent manner,leading to altered glucose uptake,lactate content and ATP production in breast cancer cells.The results of examination of embryonic fibroblasts isolated from TF20 knockout mice revealed that TF20 knockout causes increased expression levels of HK2,ALDOA and PGK1.Immunohistochemical staining demonstrated that TF20 is down-regulated in breast cancer specimens compared to adjacent normal breast cancer tissues.In summary,we found that the transcription factor TF20 is a novel regulator of glucose metabolism,which provide a new target for breast cancer diagnosis,treatment and prognosis.