Wnt activation as a therapeutic strategy in medulloblastoma.

Wnt activation as a therapeutic strategy in medulloblastoma.:

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Wnt activation as a therapeutic strategy in medulloblastoma.

Nat Commun. 2020 08 28;11(1):4323

Authors: Manoranjan B, Venugopal C, Bakhshinyan D, Adile AA, Richards L, Kameda-Smith MM, Whitley O, Dvorkin-Gheva A, Subapanditha M, Savage N, Tatari N, McKenna D, Bassey-Archibong B, Winegarden N, Hallett R, Provias JP, Yarascavitch B, Ajani O, Fleming A, Bader GD, Pugh TJ, Doble BW, Singh SK

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.



PMID: 32859895 [PubMed - indexed for MEDLINE]