ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis. Homo sapiens

Cell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation Overall design: Total RNA from primary neurosphere culture of brain tumor specimens non-treated and ST3GAL1 KD clones. The mRNAs of 5 unique glioma propagating cells (GPCs) were hybridized on Affymetrix HG-U133 Plus2 chips to study the transcriptomic impact of ST3GAL1 knock-down. Specimens were obtained from 5 glioma patients and replicate arrays were performed for all 5 neurosphere cultures.