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

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Filppu , P , Ramanathan , J T , Granberg , K J , Gucciardo , E , Haapasalo , H , Lehti , K , Nykter , M , Le Joncour , V & Laakkonen , P 2021 , ' CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity ' , JCI INSIGHT , vol. 6 , no. 9 , 141486 . https://doi.org/10.1172/jci.insight.141486

Title: CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity
Author: Filppu, Pauliina; Ramanathan, Jayendrakishore Tanjore; Granberg, Kirsi J.; Gucciardo, Erika; Haapasalo, Hannu; Lehti, Kaisa; Nykter, Matti; Le Joncour, Vadim; Laakkonen, Pirjo
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, INDIVIDRUG - Individualized Drug Therapy
University of Helsinki, Kaisa Irene Lehti / Principal Investigator
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Helsinki Institute of Life Science HiLIFE, Infra
Date: 2021-05-10
Language: eng
Number of pages: 21
Belongs to series: JCI INSIGHT
ISSN: 2379-3708
URI: http://hdl.handle.net/10138/331207
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.
Subject: GENE-EXPRESSION
NERVOUS-SYSTEM
CANCER
CD109
REVEALS
SURFACE
TUMORS
HYBRIDIZATION
ABNORMALITIES
INTERLEUKIN-6
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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