Wnt Activation As a Therapeutic Strategy in Medulloblastoma

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Aug 30

PMID 32859895

Citations 25

Authors

Branavan Manoranjan

Chitra Venugopal

David Bakhshinyan

Ashley A Adile

Laura Richards

Michelle M Kameda-Smith

Owen Whitley

Anna Dvorkin-Gheva

Minomi Subapanditha

Neil Savage

Nazanin Tatari

Dillon McKenna

Blessing Bassey-Archibong

Neil Winegarden

Robin Hallett

John P Provias

Blake Yarascavitch

Olufemi Ajani

Adam Fleming

Gary D Bader

Trevor J Pugh

Bradley W Doble

Sheila K Singh

Affiliations

Soon will be listed here.

Abstract

Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/β-catenin signaling.

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