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RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway
Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM ce...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355113/ https://www.ncbi.nlm.nih.gov/pubmed/28086236 http://dx.doi.org/10.18632/oncotarget.14564 |
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author | Adamo, Assunta Fiore, Danilo De Martino, Fabio Roscigno, Giuseppina Affinito, Alessandra Donnarumma, Elvira Puoti, Ilaria Vitiani, Lucia Ricci Pallini, Roberto Quintavalle, Cristina Condorelli, Gerolama |
author_facet | Adamo, Assunta Fiore, Danilo De Martino, Fabio Roscigno, Giuseppina Affinito, Alessandra Donnarumma, Elvira Puoti, Ilaria Vitiani, Lucia Ricci Pallini, Roberto Quintavalle, Cristina Condorelli, Gerolama |
author_sort | Adamo, Assunta |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to β-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies. |
format | Online Article Text |
id | pubmed-5355113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53551132017-04-15 RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway Adamo, Assunta Fiore, Danilo De Martino, Fabio Roscigno, Giuseppina Affinito, Alessandra Donnarumma, Elvira Puoti, Ilaria Vitiani, Lucia Ricci Pallini, Roberto Quintavalle, Cristina Condorelli, Gerolama Oncotarget Research Paper Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to β-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies. Impact Journals LLC 2017-01-09 /pmc/articles/PMC5355113/ /pubmed/28086236 http://dx.doi.org/10.18632/oncotarget.14564 Text en Copyright: © 2017 Adamo et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Adamo, Assunta Fiore, Danilo De Martino, Fabio Roscigno, Giuseppina Affinito, Alessandra Donnarumma, Elvira Puoti, Ilaria Vitiani, Lucia Ricci Pallini, Roberto Quintavalle, Cristina Condorelli, Gerolama RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title_full | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title_fullStr | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title_full_unstemmed | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title_short | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway |
title_sort | ryk promotes the stemness of glioblastoma cells via the wnt/β-catenin pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355113/ https://www.ncbi.nlm.nih.gov/pubmed/28086236 http://dx.doi.org/10.18632/oncotarget.14564 |
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