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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...

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Autores principales: Adamo, Assunta, Fiore, Danilo, De Martino, Fabio, Roscigno, Giuseppina, Affinito, Alessandra, Donnarumma, Elvira, Puoti, Ilaria, Vitiani, Lucia Ricci, Pallini, Roberto, Quintavalle, Cristina, Condorelli, Gerolama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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