Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha.

ABSTRACT:

Background

The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype.

Methods

We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo. RhoA activation, liposome binding, immunoblot, and kinase assays were utilized to elucidate the novel link between DGKα and geranylgeranyltransferase I (GGTase I).

Results

Here we show that inhibition of DGKα with a small-molecule inhibitor, ritanserin, or RN

SUBMITTER: Olmez I 

PROVIDER: S-EPMC5777487 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature