Unknown

Dataset Information

0

Estrogen-related receptor ? activation and isoform shifting by cdc2-like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma.


ABSTRACT: Glioblastoma (GBM; grade 4 glioma) is a highly aggressive and incurable tumor. GBM has recently been characterized as highly dependent on alternative splicing, a critical driver of tumor heterogeneity and plasticity. Estrogen-related receptor ? (ERR-?) is an orphan nuclear receptor expressed in the brain, where alternative splicing of the 3' end of the pre-mRNA leads to the production of 3 validated ERR-? protein products: ERR-? short form (ERR-?sf), ERR-?2, and ERR-? exon 10 deleted. Our prior studies have shown the ERR-?2 isoform to play a role in G2/M cell cycle arrest and induction of apoptosis, in contrast to the function of the shorter ERR-?sf isoform in senescence and G1 cell cycle arrest. In this study, we sought to better define the role of the proapoptotic ERR-?2 isoform in GBM. We show that the ERR-?2 isoform is located not only in the nucleus but also in the cytoplasm. ERR-?2 suppresses GBM cell migration and interacts with the actin nucleation-promoting factor cortactin, and an ERR-? agonist is able to remodel the actin cytoskeleton and similarly suppress GBM cell migration. We further show that inhibition of the splicing regulatory cdc2-like kinases in combination with an ERR-? agonist shifts isoform expression in favor of ERR-?2 and potentiates inhibition of growth and migration in GBM cells and intracranial tumors.-Tiek, D. M., Khatib, S. A., Trepicchio, C. J., Heckler, M. M., Divekar, S. D., Sarkaria, J. N., Glasgow, E., Riggins, R. B. Estrogen-related receptor ? activation and isoform shifting by cdc2-like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma.

SUBMITTER: Tiek DM 

PROVIDER: S-EPMC6894094 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3319169 | BioStudies
2015-01-01 | S-EPMC4614362 | BioStudies
2018-01-01 | S-EPMC5855702 | BioStudies
2016-01-01 | S-EPMC5216935 | BioStudies
2011-01-01 | S-EPMC3209773 | BioStudies
2009-01-01 | S-EPMC2752891 | BioStudies
2019-01-01 | S-EPMC7360104 | BioStudies
1000-01-01 | S-EPMC5761544 | BioStudies
2019-01-01 | S-EPMC6459350 | BioStudies
2015-01-01 | S-EPMC4480757 | BioStudies