Elucidating the role of PROS1 in glioma cell plasticity

Glioblastoma (GBM) is a malignant grade IV brain tumor with poor prognosis and high recurrence rates. The difficulty treating GBM arises among other reasons from the heterogenous nature of the cancer cells. The population of glioma stem cells (GSC) is thought to sustain tumor growth and confer its resistance to conventional therapies. Advances in the understanding of the genomic landscape of GBM have given rise to new and promising treatments. As part of the project to better understand the mechanisms driving cancer progression we choose to focus on proteins S (PROS1).

PROS1, an anticoagulant glycoprotein, has been implicated in various biological pathways, including those involved in cancer pathology. These functions have been investigated in several cancers, however the effect PROS1 has on GBM progression has yet to be discovered. We aim to investigate to role of PROS1 expression levels in GBM and the correlation between expression, cell state and aggressiveness of GBM.

To accomplish these goals, two constructs were used for silencing PROS1 expression; shRNA and CRISPR/cas9 (sgRNA). PROS1 KO GBM cells showed increased sensitivity to oxidative stress resulting in slower proliferation of the cells and reduced dedifferentiation abilities. Additionally, PROS1 KD cells showed compromised cell plasticity following cycles of differentiation and dedifferentiation. Tumor response to oxidative stress has been linked to chemotherapy resistance and maintenance of GSCs and these results indicate a role for PROS1 in the responsible pathways.
Shedding light on the processes driving cancer progression will contribute in the search for potential drug targets and novel therapeutic strategies.