2. Academic Validation
  3. Transcriptional control of brain tumor stem cells by a carbohydrate binding protein

Transcriptional control of brain tumor stem cells by a carbohydrate binding protein

  • Cell Rep. 2021 Aug 31;36(9):109647. doi: 10.1016/j.celrep.2021.109647.
Ahmad Sharanek 1,  Audrey Burban 1,  Aldo Hernandez-Corchado 2,  Ariel Madrigal 2,  Idris Fatakdawala 3,  Hamed S Najafabadi 2,  Vahab D Soleimani 4,  Arezu Jahani-Asl 5
Affiliations

Affiliations

  • 1 Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology and Division of Experimental Medicine, McGill University, Montréal, QC H4A 3T2, Canada.
  • 2 Department of Human Genetics, McGill University, Montréal, QC H3A OC7, Canada; McGill Genome Centre, Montréal, QC H3A 0G1, Canada.
  • 3 Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada.
  • 4 Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Department of Human Genetics, McGill University, Montréal, QC H3A OC7, Canada.
  • 5 Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology and Division of Experimental Medicine, McGill University, Montréal, QC H4A 3T2, Canada; Integrated program in Neuroscience, Montréal Neurological Institute, Montréal, QC H3A 2B4, Canada. Electronic address: arezu.jahani@mcgill.ca.
PMID: 34469737 DOI: 10.1016/j.celrep.2021.109647
Abstract

Brain tumor stem cells (BTSCs) and intratumoral heterogeneity represent major challenges in glioblastoma therapy. Here, we report that the LGALS1 gene, encoding the carbohydrate binding protein, galectin1, is a key regulator of BTSCs and glioblastoma resistance to therapy. Genetic deletion of LGALS1 alters BTSC gene expression profiles and results in downregulation of gene sets associated with the mesenchymal subtype of glioblastoma. Using a combination of pharmacological and genetic approaches, we establish that inhibition of LGALS1 signaling in BTSCs impairs self-renewal, suppresses tumorigenesis, prolongs lifespan, and improves glioblastoma response to ionizing radiation in preclinical animal models. Mechanistically, we show that LGALS1 is a direct transcriptional target of STAT3 with its expression robustly regulated by the ligand OSM. Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram the BTSC transcriptional landscape. Our data unravel an oncogenic signaling pathway by which the galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.

Keywords

EGFRvIII; HOXA5; OSM; OTX008; STAT3; galectin1; glioblastoma; glioma stem cells; ionizing radiation; mesenchymal.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19756
    99.09%, Galectin Inhibitor