2. Academic Validation
  3. CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity

CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity

  • JCI Insight. 2021 May 10;6(9):e141486. doi: 10.1172/jci.insight.141486.
Pauliina Filppu 1,  Jayendrakishore Tanjore Ramanathan 1,  Kirsi J Granberg 2 3,  Erika Gucciardo 4,  Hannu Haapasalo 5,  Kaisa Lehti 4 6 7,  Matti Nykter 2,  Vadim Le Joncour 1,  Pirjo Laakkonen 1 8
Affiliations

Affiliations

  • 1 Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • 2 Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • 3 Science Center, Tampere University Hospital, Tampere, Finland.
  • 4 Individualized Drug Therapy Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • 5 Department of Pathology, Fimlab Laboratories, Tampere University Hospital and University of Tampere, Tampere, Finland.
  • 6 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
  • 7 Department of Biomedical Laboratory Science, Faculty of Natural Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • 8 Laboratory Animal Centre, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
PMID: 33986188 DOI: 10.1172/jci.insight.141486
Abstract

Glioma stem cells (GSCs) drive propagation and therapeutic resistance of glioblastomas, the most aggressive diffuse brain tumors. However, the molecular mechanisms that maintain the stemness and promote therapy resistance remain poorly understood. Here we report CD109/STAT3 axis as crucial for the maintenance of stemness and tumorigenicity of GSCs and as a mediator of chemoresistance. Mechanistically, CD109 physically interacts with glycoprotein 130 to promote activation of the IL-6/STAT3 pathway in GSCs. Genetic depletion of CD109 abolished the stemness and self-renewal of GSCs and impaired tumorigenicity. Loss of stemness was accompanied with a phenotypic shift of GSCs to more differentiated astrocytic-like cells. Importantly, genetic or pharmacologic targeting of CD109/STAT3 axis sensitized the GSCs to chemotherapy, suggesting that targeting CD109/STAT3 axis has potential to overcome therapy resistance in glioblastoma.

Keywords

Brain cancer; Molecular biology; Molecular pathology; Oncology; Stem cells.

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