Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells.

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. Cancer Res; 77(4); 996-1007. ©2016 AACR.

journal_name

Cancer Res

journal_title

Cancer research

authors

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 AL

doi

10.1158/0008-5472.CAN-16-1693

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

996-1007

issue

4

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-16-1693

journal_volume

77

pub_type

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