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CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity
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 m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262342/ https://www.ncbi.nlm.nih.gov/pubmed/33986188 http://dx.doi.org/10.1172/jci.insight.141486 |
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author | Filppu, Pauliina Tanjore Ramanathan, Jayendrakishore Granberg, Kirsi J. Gucciardo, Erika Haapasalo, Hannu Lehti, Kaisa Nykter, Matti Le Joncour, Vadim Laakkonen, Pirjo |
author_facet | Filppu, Pauliina Tanjore Ramanathan, Jayendrakishore Granberg, Kirsi J. Gucciardo, Erika Haapasalo, Hannu Lehti, Kaisa Nykter, Matti Le Joncour, Vadim Laakkonen, Pirjo |
author_sort | Filppu, Pauliina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8262342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-82623422021-07-13 CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity Filppu, Pauliina Tanjore Ramanathan, Jayendrakishore Granberg, Kirsi J. Gucciardo, Erika Haapasalo, Hannu Lehti, Kaisa Nykter, Matti Le Joncour, Vadim Laakkonen, Pirjo JCI Insight Research Article 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. American Society for Clinical Investigation 2021-05-10 /pmc/articles/PMC8262342/ /pubmed/33986188 http://dx.doi.org/10.1172/jci.insight.141486 Text en © 2021 Filppu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Filppu, Pauliina Tanjore Ramanathan, Jayendrakishore Granberg, Kirsi J. Gucciardo, Erika Haapasalo, Hannu Lehti, Kaisa Nykter, Matti Le Joncour, Vadim Laakkonen, Pirjo CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title | CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title_full | CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title_fullStr | CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title_full_unstemmed | CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title_short | CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity |
title_sort | cd109-gp130 interaction drives glioblastoma stem cell plasticity and chemoresistance through stat3 activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262342/ https://www.ncbi.nlm.nih.gov/pubmed/33986188 http://dx.doi.org/10.1172/jci.insight.141486 |
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