Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program

Frontiers in Oncology

Rhishikesh Bargaje¹  Lucy Lu²  Amit S. Adhikari²  T Norene O’Sullivan²  Terry Van Dyke²  Yurong Song²  Teresa Sullivan² 

[1] Institute for Systems Biology, Seattle, WA, United States;Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States;

关键词: glioblastoma/astrocytoma;    retinoblastoma tumor suppression;    progenitors;    cancer initiating cells;    KRAS;    cancer initiation;   

DOI  :  10.3389/fonc.2022.904479

来源: DOAJ

【 摘 要 】

Glioblastoma (GBM) remains lethal with no effective treatments. Despite the comprehensive identification of commonly perturbed molecular pathways, little is known about the disease’s etiology, particularly in early stages. Several studies indicate that GBM is initiated in neural progenitor and/or stem cells. Here, we report that differentiated astrocytes are susceptible to GBM development when initiated by perturbation of the RB pathway, which induces a progenitor phenotype. In vitro and in vivo inactivation of Rb tumor suppression (TS) induces cortical astrocytes to proliferate rapidly, express progenitor markers, repress differentiation markers, and form self-renewing neurospheres that are susceptible to multi-lineage differentiation. This phenotype is sufficient to cause grade II astrocytomas which stochastically progress to GBM. Together with previous findings, these results demonstrate that cell susceptibility to GBM depends on the initiating driver.

【 授权许可】

Unknown