Genomics

Dataset Information

33

Wnt5a Drives The State Transition To An Invasive Phenotype In Human Glioblastoma Cancer Stem Cells


ABSTRACT: Numerous pathways underlie brain invasion by tumors, a critical element underpinning recurrence and lethality in human glioblastomas (hGBMs). The identification of the master factors that elicit these pathways globally, driving invasion altogether, eludes us. We report that high expression levels of non-canonical Wnt5a characterize the most invasive gliomas, epitomize dismal prognosis and discriminate the most infiltrating mesenchymal hGBMs from proneural and classical ones. Exacerbated Wnt5a defines mesenchymal hGBM cells (Wnt5aHigh) possessing prototypical invasiveness and tumor-promoting stem-like characteristics (TPCs), but not their Wnt5aLow siblings. While inhibition of Wnt5a suppresses infiltration in mesenchymal hGBM TPCs, administration or over-expression of Wnt5a elicits the opposite effects, turning on infiltrative “mesenchymal-like” molecular programs in poorly motile, classical hGBM TPCs and Wnt5aLow mesenchymal TPCs, ex vivo and intracranially. Anti-Wnt5a antibodies or antagonist Wnt5a peptides block invasion, increasing survival in clinically relevant intracranial hGBM models. Wnt5a emerges as a master regulator in gliomatous invasion, endowing hGBM TPCs with archetypal, infiltratory transcriptional and functional profiles, providing a unique target to tackle brain invasion by hGBM cancer stem cells. Overall design: A total of 12 samples were analyzed. Each experimental group was made of two biological replicates. Each biological replicate had two technical replicates. Sorted hGBM specimens were compared with unsorted hGBM specimens.

INSTRUMENT(S): [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]

SUBMITTER: Tommaso Mazza 

PROVIDER: GSE76422 | GEO | 2017-03-07

SECONDARY ACCESSION(S): PRJNA307251

REPOSITORIES: GEO

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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 g  ...[more]

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