RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway

Assunta Adamo, Danilo Fiore, Fabio De Martino, Giuseppina Roscigno, Alessandra Affinito, Elvira Donnarumma, Ilaria Puoti, Lucia Ricci Vitiani, Roberto Pallini, Cristina Quintavalle, Gerolama Condorelli

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Abstract

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.

Original languageEnglish
Pages (from-to)13476-13487
Number of pages12
JournalOncotarget
Volume8
Issue number8
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • Glioblastoma
  • Ryk
  • Stem cells
  • β-catenin

ASJC Scopus subject areas

  • Oncology

Cite this

Adamo, A., Fiore, D., De Martino, F., Roscigno, G., Affinito, A., Donnarumma, E., Puoti, I., Vitiani, L. R., Pallini, R., Quintavalle, C., & Condorelli, G. (2017). RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway. Oncotarget, 8(8), 13476-13487. https://doi.org/10.18632/oncotarget.14564