Wnt5a drives an invasive phenotype in human glioblastoma stem-like cells

Elena Binda, Alberto Visioli, Fabrizio Giani, Nadia Trivieri, Orazio Palumbo, Silvia Restelli, Fabio Dezi, Tommaso Mazza, Caterina Fusilli, Federico Legnani, Massimo Carella, Francesco Di Meco, Rohit Duggal, Angelo L. Vescovi

Research output: Contribution to journalArticle

Abstract

Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a.We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5aHigh). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma.

Original languageEnglish (US)
Pages (from-to)996-1007
Number of pages12
JournalCancer Research
Volume77
Issue number4
DOIs
StatePublished - Feb 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Binda, E., Visioli, A., Giani, F., Trivieri, N., Palumbo, O., Restelli, S., Dezi, F., Mazza, T., Fusilli, C., Legnani, F., Carella, M., Di Meco, F., Duggal, R., & Vescovi, A. L. (2017). Wnt5a drives an invasive phenotype in human glioblastoma stem-like cells. Cancer Research, 77(4), 996-1007. https://doi.org/10.1158/0008-5472.CAN-16-1693