CREB1 Regulates Glucose Transport Of Glioma Cells And The Related Molecular Mechanism

Glioma is one of the most common intracranial tumors in the brain,which accounts for 45% of all intracranial tumors.The growth characteristics of glioma are infiltrative growth and no obvious boundaries from normal brain tissues.Furthermore,it is difficult to remove completely,easy to relapse and not sensitive to radiotherapy and chemotherapy,so glioma is still one of the worst prognosis of systemic cancer tumor.Tumor cells relies on glycolysis to obtain energy and sustain their survival under low glucose and low oxgen microenvironment in vivo.In order to adapt to hypoxia and compete with normal cells,they exhibit a unique metabolic pattern,named Warburg effect.The best-know metabolic abnormality of glioma is Warburg effect.Althrough there are many researches on Warburg effect,the incidence and development of this metabolism is still unclear.GLUT1(Glucose transporter 1)an important glucose uniporter,is related to the Warburg effect,but it is still not very clear of the molecular mechanism.CREB1(cAMP responsive element binding protein 1),the protein which can regulate the transcription of gene,is named transcriptional enhancer.It is involved in various cellular signaling pathways and the evolution of multiple tumors.Firstly,we detected the expression of CREB1 and GLUT1 protein by immunohistochemistry and bioinformatics.Immunohistochemical results showed that: The expression of CREB1 and GLUT1 in glioma tissues was significantly higher than normal tissues,and the expression level is increaseing with the tumor progression.The gene chips were collected and calculated.The results show that CREB1 and GLUT1 showed high expression in glioma;we used RNA interference to knockdown the CREB1 in U87 and U251,found that the experssion of GLUT1 is down regulation and the uptake of glucose is also reducing.CREB1,cAMP responsive element-binding protein,is activated by phosphorylation.Therefore,we regulate the phosphorylation of CREB1 by H89 inhibitor and forskolin activator.The results show that: When we use H89 to treat cells,compared with the normal group,the glucose absorption of cells is decreasing and the expression of GLUT1 is down regulation;but when we use forskolin to treat cells,compared with the normal group,the glucose absorption of cells is increasing and the expression of GLUT1 is up regulation.These data indicate that the relationship between the CREB1 and GLUT1 is the crucial element in glioma glucose transport.This study investigates the role of CREB1 in the glucose transport of U87 and U251 in malignant glioma cell lines in vitro.CREB1,an important transcription factor of cAMP second messenger pathway,plays an important role in signal transduction.According to some researches,the cAMP second messenger pathway medias the glucose transportion of tumor.We make the CREB1 as the breakthrough point,in term of expression of GLUT1,we study the glucose transportion of glioma,which probably privates a target for treatment of glioma.