ASCL1 Phosphorylation and ID2 Upregulation Are Roadblocks to Glioblastoma Stem Cell Differentiation

Overview

Journal Sci Rep

Specialty Science

Date 2022 Feb 12

PMID 35149717

Authors

Roberta Azzarelli

Aoibheann McNally

Claudia DellAmico

Marco Onorati

Benjamin Simons

Anna Philpott

Affiliations

Soon will be listed here.

Abstract

The growth of glioblastoma (GBM), one of the deadliest adult cancers, is fuelled by a subpopulation of stem/progenitor cells, which are thought to be the source of resistance and relapse after treatment. Re-engagement of a latent capacity of these cells to re-enter a trajectory resulting in cell differentiation is a potential new therapeutic approach for this devastating disease. ASCL1, a proneural transcription factor, plays a key role in normal brain development and is also expressed in a subset of GBM cells, but fails to engage a full differentiation programme in this context. Here, we investigated the barriers to ASCL1-driven differentiation in GBM stem cells. We see that ASCL1 is highly phosphorylated in GBM stem cells where its expression is compatible with cell proliferation. However, overexpression of a form of ASCL1 that cannot be phosphorylated on Serine-Proline sites drives GBM cells down a neuronal lineage and out of cell cycle more efficiently than its wild-type counterpart, an effect further enhanced by deletion of the inhibitor of differentiation ID2, indicating mechanisms to reverse the block to GBM cell differentiation.

Citing Articles

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