{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gong AH"],"funding":["NCATS NIH HHS","NCI NIH HHS"],"pagination":["2337-48"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4452436"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["75(11)"],"pubmed_abstract":["The growth factor PDGF controls the development of glioblastoma (GBM), but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here, we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM, we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database The Cancer Genome Atlas revealed that GBM expresses higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells."],"journal":["Cancer research"],"pubmed_title":["FoxM1 Drives a Feed-Forward STAT3-Activation Signaling Loop That Promotes the Self-Renewal and Tumorigenicity of Glioblastoma Stem-like Cells."],"pmcid":["PMC4452436"],"funding_grant_id":["R01 CA182684","R01CA157933","UL1 TR000371","R21 CA152623","P50 CA127001","R01CA182684","P50CA127001","R01 CA157933","R21CA152623"],"pubmed_authors":["Wei P","Yao J","Huang S","Heimberger AB","Zhou AD","Rao G","Gong AH","Zhang S","Yuan Y","Lang FF"],"additional_accession":[]},"is_claimable":false,"name":"FoxM1 Drives a Feed-Forward STAT3-Activation Signaling Loop That Promotes the Self-Renewal and Tumorigenicity of Glioblastoma Stem-like Cells.","description":"The growth factor PDGF controls the development of glioblastoma (GBM), but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here, we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM, we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database The Cancer Genome Atlas revealed that GBM expresses higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jun","modification":"2026-04-13T08:26:40.02Z","creation":"2019-03-27T01:52:36Z"},"accession":"S-EPMC4452436","cross_references":{"pubmed":["25832656"],"doi":["10.1158/0008-5472.can-14-2800","10.1158/0008-5472.CAN-14-2800"]}}