2017
DOI: 10.1016/j.celrep.2016.12.064
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Abstract: SUMMARY Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify a SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and is capable of driving glioma initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc finger E-box binding homeobox 1 (ZEB1) as potential SOX2 targets, which are frequently co-expres… Show more

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Cited by 77 publications
(95 citation statements)
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References 39 publications
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“…We and others have shown that ZEB1 is a key regulator of stemness, invasion and chemoresistance in GBM (7,12,42), and consistently we find that ZEB1 mediates the stemness effects of FGF2/FGFR1 signaling. Singh and colleagues have recently demonstrated that ZEB1, SOX2 and OLIG2 form an autonomous transcriptional loop in GBM, and can regulate their expression reciprocally (26). Our data supports this, as the FGF2/FGFR1 complex activates expression of SOX2 and OLIG2 in our system as well, and ZEB1, SOX2, and OLIG2 are linked in hierarchical cluster analysis of TCGA data.…”
Section: Discussionsupporting
confidence: 87%
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“…We and others have shown that ZEB1 is a key regulator of stemness, invasion and chemoresistance in GBM (7,12,42), and consistently we find that ZEB1 mediates the stemness effects of FGF2/FGFR1 signaling. Singh and colleagues have recently demonstrated that ZEB1, SOX2 and OLIG2 form an autonomous transcriptional loop in GBM, and can regulate their expression reciprocally (26). Our data supports this, as the FGF2/FGFR1 complex activates expression of SOX2 and OLIG2 in our system as well, and ZEB1, SOX2, and OLIG2 are linked in hierarchical cluster analysis of TCGA data.…”
Section: Discussionsupporting
confidence: 87%
“…We next sought to define how FGF2 acts on GSCs by testing whether FGF2 correlated with the GSC-associated transcription factors ZEB1, SOX2, or OLIG2 (26). Using TCGA gene expression data, we found each of these transcription factors correlated strongly with FGF2 ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In addition, mithramycin A inhibits a SOX2-dependent transcriptional regulatory network, leading to reduced proliferation of GBM cells in vivo. The data warrant further testing of mithramycin A in preclinical GBM models (Singh et al 2017). At the same time, our data suggest further experiments addressing the impact of mithramycin A on the expression of MGMT and the toxicity of TMZ in MGMT expressing cells.…”
mentioning
confidence: 54%
“…The data warrant further testing of mithramycin A in preclinical GBM models (Singh et al . ). At the same time, our data suggest further experiments addressing the impact of mithramycin A on the expression of MGMT and the toxicity of TMZ in MGMT expressing cells.…”
Section: Discussionmentioning
confidence: 97%
“…Based on their known activities, aureolic acids have been pursued as anti-cancer chemotherapies. For example, these compounds have been implicated as anti-tumor agents (15,19), inhibitors of Wnt signaling (20) and DNA gyrase (21), as well as autophagy inducers (22,23), although the specific genes and pathways implicated in the mechanism of action of CMA2 and MTM are only just being fleshed out.…”
Section: Introductionmentioning
confidence: 99%