American Association for Cancer Research
00085472can161693-sup-168041_2_supp_3739905_8ghn8j.pdf (5.09 MB)

Supplementary Figures from Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

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journal contribution
posted on 2023-03-31, 01:10 authored by 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

Suppl Fig S1: Levels of Wnt5a expression in brain tumors correlate to aggressiveness or outcome; Suppl Fig S2: Wnt5a overexpression sustains TPCs invasive capability; Suppl Fig S3: Elevated Wnt5a expression promotes migratory capability in otherwise poorly motile U87MG, both in vitro and in vivo; Suppl Fig S4: Pathways enrichment of invasive TPCs progeny based on Wnt5a levels; Suppl Fig S5: Mesenchymal hGBM TPCs are endowed with enhanced dispersal ability to distribute widely in the brain as compared to classical TPCs; Suppl Fig S6: Hypothetical mechanism of Wnt5a regulation that confers the infiltratory phenotype in hGBM TPCs;


Associazione Italiana per la Ricerca sul Cancro


Ministero della Salute Italiano

Progetto Operativo Nazionale



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.

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