Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,incl...Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and dif-ferentiation.FGFR1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall survival.We rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro.CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1.CYY292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene knockdown.In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547.CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models.This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.展开更多
The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB str...The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image selection.Additionally,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image selection.We have attached the original data to show that this was also an unintentional error.We assure you that these two corrections do not alter the scientificconclusionof thearticle.展开更多
基金supported by the National Natural Science Foundation of China(No.81971180,81973168 and 82003793)CAMS Innovation Fund for Medical Sciences(No.2019-12M-5-028)+1 种基金the Scientific Research Project of Wenzhou,Zhejiang,China(No.ZY2019001)the National Natural Science Foundation of Zhejiang Province,China(No.LZ22H300002).
文摘Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and dif-ferentiation.FGFR1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall survival.We rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro.CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1.CYY292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene knockdown.In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547.CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models.This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.
文摘The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image selection.Additionally,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image selection.We have attached the original data to show that this was also an unintentional error.We assure you that these two corrections do not alter the scientificconclusionof thearticle.
