Transcriptional Control of Brain Tumour Stem Cell Fate by a Carbohydrate Binding Protein

Brain tumour stem cells (BTSC) and intratumoural heterogeneity represent major challenges for the effective treatment of glioblastoma. EGFRvIII is a key oncogenic protein in glioblastoma, however, the mechanisms that regulate BTSC fate in EGFRvIII subtype of tumours remain poorly characterized. Here, we report our discovery of the lectin, galactoside-binding, soluble 1 (LGALS1) gene, encoding the carbohydrate binding protein, galectin1, as a key regulator of BTSC fate in glioblastoma tumours harbouring the EGFRvIII mutation. Genetic deletion of LGALS1 alters gene expression profile of BTSCs, leads to cell cycle defects and impairs self-renewal. Using a combination of pharmacological and genetic approaches in preclinical animal models, we establish that inhibition of LGALS1 signalling in BTSCs suppresses tumourigenesis, prolongs lifespan, and improves glioblastoma response to radiation-therapy. Mechanistically, two key transcription factors are involved in the regulation of LGALS1 expression and function. Upstream, STAT3 directly binds to the promoter of LGALS1 and robustly upregulates its expression. Downstream, galectin1 forms a complex with the transcription factor homeobox5 (HOXA5) to reprogram BTSC transcriptional landscape and drive glioblastoma tumourigenesis. Our data unravel a novel LGALS1/HOXA5 oncogenic signalling pathway that is required for BTSC maintenance and the pathogenesis of EGFRvIII subtype of glioblastoma.

The A to B of starch granule formation in wheat endosperm

This article comments on: Chia T, Chirico M, King R et al. 2019. A carbohydrate-binding protein, B-granule content 1 influences starch granule-size distribution in a dose dependent manner in polyploid wheat. Journal of Experimental Botany 70, 105–115.

Effects of microvirin monomers and oligomers on hepatitis C virus

Microvirin (MVN) is a carbohydrate-binding protein which shows high specificity for high-mannose type N-glycan structures. In the present study, we tried to identify whether MVN could bind to high-mannose containing hepatitis C virus (HCV) envelope glycoproteins, which are heavily decorated high-mannose glycans. In addition, recombinantly expressed MVN oligomers in di-, tri- and tetrameric form were evaluated for their viral inhibition. MVN oligomers bound more efficiently to HCV virions, and displayed in comparison with the MVN monomer a higher neutralization potency against HCV infection. The antiviral effect was furthermore affected by the peptide linker sequence connecting the MVN monomers. The results indicate that MVN oligomers such as trimers and tetramers may be used as future neutralization agents against HCV infections.